NM_000463.3(UGT1A1):c.575A>G (p.Tyr192Cys) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 8, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000315749.6

Allele description [Variation Report for NM_000463.3(UGT1A1):c.575A>G (p.Tyr192Cys)]

NM_000463.3(UGT1A1):c.575A>G (p.Tyr192Cys)

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.575A>G (p.Tyr192Cys)
HGVS:
  • NC_000002.12:g.233760862A>G
  • NG_002601.2:g.176119A>G
  • NG_033238.1:g.5590A>G
  • NM_000463.3:c.575A>GMANE SELECT
  • NM_001072.4:c.862-6172A>GMANE SELECT
  • NM_007120.3:c.868-6172A>GMANE SELECT
  • NM_019075.4:c.856-6172A>GMANE SELECT
  • NM_019076.5:c.856-6172A>GMANE SELECT
  • NM_019077.3:c.856-6172A>GMANE SELECT
  • NM_019078.2:c.868-6172A>GMANE SELECT
  • NM_019093.4:c.868-6172A>GMANE SELECT
  • NM_021027.3:c.856-6172A>GMANE SELECT
  • NM_205862.3:c.61-6172A>G
  • NP_000454.1:p.Tyr192Cys
  • NP_000454.1:p.Tyr192Cys
  • LRG_733t1:c.575A>G
  • LRG_733:g.5590A>G
  • LRG_733p1:p.Tyr192Cys
  • NC_000002.11:g.234669508A>G
  • NM_000463.2:c.575A>G
Protein change:
Y192C
Links:
dbSNP: rs201093245
NCBI 1000 Genomes Browser:
rs201093245
Molecular consequence:
  • NM_001072.4:c.862-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007120.3:c.868-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019075.4:c.856-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019076.5:c.856-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019077.3:c.856-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019078.2:c.868-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_019093.4:c.868-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_021027.3:c.856-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_205862.3:c.61-6172A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000463.3:c.575A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000336553Eurofins Ntd Llc (ga)
criteria provided, single submitter

(EGL Classification Definitions 2015)		Uncertain significance
(Oct 28, 2015) 		germlineclinical testing

Citation Link,

SCV003305837Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 8, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot providednot providednot providedclinical 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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Eurofins Ntd Llc (ga), SCV000336553.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV003305837.2

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

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 192 of the UGT1A1 protein (p.Tyr192Cys). This variant is present in population databases (rs201093245, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with UGT1A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 284079). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt UGT1A1 protein function with a positive predictive value of 80%. 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.

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

Last Updated: Sep 1, 2024