NM_001371623.1(TCOF1):c.3658T>C (p.Ser1220Pro) AND Treacher Collins syndrome 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 28, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002918378.2

Allele description [Variation Report for NM_001371623.1(TCOF1):c.3658T>C (p.Ser1220Pro)]

NM_001371623.1(TCOF1):c.3658T>C (p.Ser1220Pro)

Gene:

TCOF1:treacle ribosome biogenesis factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_001371623.1(TCOF1):c.3658T>C (p.Ser1220Pro)

HGVS:

NC_000005.10:g.150393426T>C
NG_011341.1:g.40788T>C
NM_000356.4:c.3424T>C
NM_001135243.2:c.3655T>C
NM_001135244.2:c.3544T>C
NM_001135245.2:c.3427T>C
NM_001195141.2:c.3541T>C
NM_001371623.1:c.3658T>CMANE SELECT
NP_000347.2:p.Ser1142Pro
NP_001128715.1:p.Ser1219Pro
NP_001128716.1:p.Ser1182Pro
NP_001128717.1:p.Ser1143Pro
NP_001182070.1:p.Ser1181Pro
NP_001358552.1:p.Ser1220Pro
NC_000005.9:g.149772989T>C

Protein change:

S1142P

Molecular consequence:

NM_000356.4:c.3424T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001135243.2:c.3655T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001135244.2:c.3544T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001135245.2:c.3427T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001195141.2:c.3541T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001371623.1:c.3658T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Treacher Collins syndrome 1 (TCS1)
Identifiers:: MONDO: MONDO:0007944; MedGen: CN315775; Orphanet: 861; OMIM: 154500

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003256587	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 28, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003256587

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 28, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003256587.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1219 of the TCOF1 protein (p.Ser1219Pro). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 2047883). This variant has not been reported in the literature in individuals affected with TCOF1-related conditions. This variant is present in population databases (rs746397186, gnomAD 0.008%).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 20, 2024

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