ClinVar Genomic variation as it relates to human health
NM_001365902.3(NFIX):c.317C>T (p.Ser106Phe)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001365902.3(NFIX):c.317C>T (p.Ser106Phe)
Variation ID: 1805245 Accession: VCV001805245.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.13 19: 13025310 (GRCh38) [ NCBI UCSC ] 19: 13136124 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 24, 2022 Dec 24, 2022 Feb 2, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001365902.3:c.317C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001352831.1:p.Ser106Phe missense NM_001271043.2:c.341C>T NP_001257972.1:p.Ser114Phe missense NM_001271044.3:c.293C>T NP_001257973.1:p.Ser98Phe missense NM_001365982.2:c.317C>T NP_001352911.1:p.Ser106Phe missense NM_001365983.2:c.176C>T NP_001352912.1:p.Ser59Phe missense NM_001365984.2:c.314C>T NP_001352913.1:p.Ser105Phe missense NM_001365985.2:c.314C>T NP_001352914.1:p.Ser105Phe missense NM_001378404.1:c.293C>T NP_001365333.1:p.Ser98Phe missense NM_001378405.1:c.365C>T NP_001365334.1:p.Ser122Phe missense NM_002501.4:c.317C>T NP_002492.2:p.Ser106Phe missense NC_000019.10:g.13025310C>T NC_000019.9:g.13136124C>T NG_032925.2:g.34541C>T NG_140480.1:g.522C>T - Protein change
- S105F, S106F, S114F, S122F, S59F, S98F
- Other names
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- Canonical SPDI
- NC_000019.10:13025309:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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NFIX | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
382 | 413 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Feb 2, 2022 | RCV002471663.1 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Feb 02, 2022)
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criteria provided, single submitter
Method: clinical testing
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Malan overgrowth syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002769107.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Sotos syndrome 2 (MIM#614753) (also known as Malan overgrowth syndrome, MONDO#0013885) and dominant negative is a suspected mechanism for Marshall-Smith syndrome (MIM#602535) (PMID: 24924640). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from serine to phenylalanine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0602 - Variant is located in a hotspot region. Malan overgrowth syndrome is caused by deletions or missense mutations clustered mostly in exon 2 (PMID: 29897170). (SP) 0704 - Another missense variant comparable to the one identified in this case has limited previous evidence for pathogenicity. An alternative change to a proline has been reported once as likely pathogenic in ClinVar. (SP) 0803 - This variant has limited previous evidence of pathogenicity in two unrelated individuals, one with macrocephaly and moderate intellectual disability and the other one with Malan syndrome (PMID: 28475857, 29897170). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Further delineation of Malan syndrome. | Priolo M | Human mutation | 2018 | PMID: 29897170 |
Mutations in Epigenetic Regulation Genes Are a Major Cause of Overgrowth with Intellectual Disability. | Tatton-Brown K | American journal of human genetics | 2017 | PMID: 28475857 |
Deletions in the 3' part of the NFIX gene including a recurrent Alu-mediated deletion of exon 6 and 7 account for previously unexplained cases of Marshall-Smith syndrome. | Schanze D | Human mutation | 2014 | PMID: 24924640 |
Text-mined citations for this variant ...
HelpRecord last updated Jan 26, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.