NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln) AND not specified

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Jun 19, 2020
Review status:: criteria provided, conflicting classifications

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:: RCV000147905.4

Allele description

NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln)

Genes:

UGT1A:UDP glucuronosyltransferase family 1 member A complex locus [Gene - HGNC]
UGT1A10:UDP glucuronosyltransferase family 1 member A10 [Gene - OMIM - HGNC]
UGT1A1:UDP glucuronosyltransferase family 1 member A1 [Gene - OMIM - HGNC]
UGT1A3:UDP glucuronosyltransferase family 1 member A3 [Gene - OMIM - HGNC]
UGT1A4:UDP glucuronosyltransferase family 1 member A4 [Gene - OMIM - HGNC]
UGT1A5:UDP glucuronosyltransferase family 1 member A5 [Gene - OMIM - HGNC]
UGT1A6:UDP glucuronosyltransferase family 1 member A6 [Gene - OMIM - HGNC]
UGT1A7:UDP glucuronosyltransferase family 1 member A7 [Gene - OMIM - HGNC]
UGT1A8:UDP glucuronosyltransferase family 1 member A8 [Gene - OMIM - HGNC]
UGT1A9:UDP glucuronosyltransferase family 1 member A9 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.1

Genomic location:

Preferred name:

NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln)

HGVS:

NC_000002.12:g.233760973C>A
NG_002601.2:g.176230C>A
NG_033238.1:g.5701C>A
NM_000463.2:c.686C>A
NM_000463.3:c.686C>AMANE SELECT
NM_001072.4:c.862-6061C>AMANE SELECT
NM_007120.3:c.868-6061C>AMANE SELECT
NM_019075.4:c.856-6061C>AMANE SELECT
NM_019076.5:c.856-6061C>AMANE SELECT
NM_019077.3:c.856-6061C>AMANE SELECT
NM_019078.2:c.868-6061C>AMANE SELECT
NM_019093.4:c.868-6061C>AMANE SELECT
NM_021027.3:c.856-6061C>AMANE SELECT
NM_205862.3:c.61-6061C>A
NP_000454.1:p.Pro229Gln
NP_000454.1:p.Pro229Gln
LRG_733t1:c.686C>A
LRG_733:g.5701C>A
LRG_733p1:p.Pro229Gln
NC_000002.11:g.234669619C>A
NC_000002.11:g.234669619C>A
P22309:p.Pro229Gln

Protein change:

P229Q; PRO229GLN

Links:

UniProtKB: P22309#VAR_009505; OMIM: 191740.0010; dbSNP: rs35350960

NCBI 1000 Genomes Browser:

rs35350960

Molecular consequence:

NM_001072.4:c.862-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_007120.3:c.868-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019075.4:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019076.5:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019077.3:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019078.2:c.868-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_019093.4:c.868-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_021027.3:c.856-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_205862.3:c.61-6061C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000463.2:c.686C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_000463.3:c.686C>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000195396	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2007)	Benign (Feb 8, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001653054	Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jun 19, 2020)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 15304120, 9621515, 7715297, 12181437, 29137095, 8528206, 18004206, 25755387, 31467903, 30544479, 14616765, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000195396

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2007)

Benign
(Feb 8, 2013)

germline

clinical testing

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

SCV001653054

Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jun 19, 2020)

germline

clinical testing

PubMed (12)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Genetic polymorphisms of bilirubin uridine diphosphate-glucuronosyltransferase gene in Japanese patients with Crigler-Najjar syndrome or Gilbert's syndrome as well as in healthy Japanese subjects.

Takeuchi K, Kobayashi Y, Tamaki S, Ishihara T, Maruo Y, Araki J, Mifuji R, Itani T, Kuroda M, Sato H, Kaito M, Adachi Y.

J Gastroenterol Hepatol. 2004 Sep;19(9):1023-8.

PubMed [citation]

PMID:: 15304120

See all PubMed Citations (13)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV000195396.1

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

#	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

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV001653054.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (12)

Description

The p.Pro229Gln variant in UGT1A1 has been reported in the heterogygous and compound heterozygous state in numerous individuals with Gilbert syndrome or Crigler-Najjar syndrome type II , however, most of them were also homozygous for other pathogenic variants in the gene. This variant has also been reported in ClinVar (Variation ID 12274). It has been identified in 1.9% (389/19954) of East Asian chromosomes by gnomAD (https://gnomad.broadinstitute.org/). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In vitro functional studies provide some evidence that this variant impacts protein function (Gagne 2002 PMID: 12181437, Udomuksorn 2007 PMID: 18004206); however, these types of assays may not accurately represent biological function. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PS3_Supporting, BS1_Supporting, BP4.

#	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		1	not provided	1	not provided

Last Updated: Oct 25, 2021

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