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NM_000463.3(UGT1A1):c.686C>A (p.Pro229Gln) AND UGT1A1-related condition

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 8, 2024
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:
RCV003390674.5

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_000463.3: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
  • NM_000463.2:c.686C>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_000463.3:c.686C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
UGT1A1-related condition
Identifiers:

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004120217PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Feb 8, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004120217.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The UGT1A1 c.686C>A variant is predicted to result in the amino acid substitution p.Pro229Gln. The minor allele frequency of this variant is over 1% in the East Asian sub-population, including 3 homozygotes, indicating this variant may be too common to be a primary cause of a Mendelian disease. However, an in vitro study indicated this variant caused a reduction in the activity of bilirubin UDP-glucuronosyltransferase (UGT) (Koiwai et al. 1995. PubMed ID: 8528206). The contribution of this variant to disease remains under debate (Kaniwa et al. 2005. PubMed ID: 15572581; Zhang et al. 2007. PubMed ID: 17060921; Wisnumurti et al. 2018. PubMed ID: 29607327), and classifications for this variant from outside laboratories range from benign to pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/12274/). Therefore, we classify c.686C>A (p.Pro229Gln) as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024