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NM_001128425.2(MUTYH):c.37G>A (p.Ala13Thr) AND Carcinoma of colon

Germline classification:
Uncertain significance (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000502616.2

Allele description [Variation Report for NM_001128425.2(MUTYH):c.37G>A (p.Ala13Thr)]

NM_001128425.2(MUTYH):c.37G>A (p.Ala13Thr)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001128425.2(MUTYH):c.37G>A (p.Ala13Thr)
HGVS:
  • NC_000001.11:g.45334511C>T
  • NG_008189.1:g.10960G>A
  • NM_001048171.2:c.-6G>A
  • NM_001048172.2:c.-6G>A
  • NM_001048173.2:c.-6G>A
  • NM_001048174.2:c.-6G>AMANE SELECT
  • NM_001128425.2:c.37G>A
  • NM_001293190.2:c.37G>A
  • NM_001293191.2:c.-6G>A
  • NM_001293192.2:c.-218G>A
  • NM_001293195.2:c.-6G>A
  • NM_001293196.2:c.-218G>A
  • NM_001350650.2:c.-277G>A
  • NM_001350651.2:c.-213G>A
  • NM_012222.3:c.37G>A
  • NP_001121897.1:p.Ala13Thr
  • NP_001121897.1:p.Ala13Thr
  • NP_001280119.1:p.Ala13Thr
  • NP_036354.1:p.Ala13Thr
  • LRG_220t1:c.37G>A
  • LRG_220:g.10960G>A
  • LRG_220p1:p.Ala13Thr
  • NC_000001.10:g.45800183C>T
  • NM_001128425.1:c.37G>A
  • NR_146882.2:n.223G>A
  • NR_146883.2:n.146G>A
Protein change:
A13T
Links:
dbSNP: rs375349172
NCBI 1000 Genomes Browser:
rs375349172
Molecular consequence:
  • NM_001048171.2:c.-6G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001048172.2:c.-6G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001048173.2:c.-6G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001048174.2:c.-6G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293191.2:c.-6G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293192.2:c.-218G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293195.2:c.-6G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001293196.2:c.-218G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350650.2:c.-277G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350651.2:c.-213G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001128425.2:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.37G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.223G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.146G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Name:
Carcinoma of colon (CRC)
Synonyms:
Colonic carcinoma; Colon carcinoma
Identifiers:
MONDO: MONDO:0002032; MedGen: C0699790

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000592672Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Uncertain significanceunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592672.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The p.Ala13Thr variant was identified in the literature in 1 of 156 proband chromosomes from individuals with mixed CRC phenotypes and was not identified in 20 control chromosomes (Tricarico 2011); however, this limited set of cases and controls is not sufficient to be able to predict the significance of this variant. This variant was identified by the ESP in 1 of 8600 chromsomes (frequency of 0.0001); this limited number of observations is not sufficient to determine whether or not this is a low frequency common benign variant or a rare pathogenic variant. The p.Al13 residue is not present in all mammals and computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. The p.Al13Thr (c.37G>A) variant occurs in the first base of the exon and this position has been shown to be part of the splicing consensus sequence and variants involving this position sometimes affect splicing. However, splicing in-silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) does not predict a significant difference in splicing in 3 of 5 different programs. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of unknown significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Jun 23, 2024