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NM_017662.5(TRPM6):c.499G>T (p.Ala167Ser) AND not provided

Germline classification:
Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:
Dec 19, 2023
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:
RCV000658047.8

Allele description [Variation Report for NM_017662.5(TRPM6):c.499G>T (p.Ala167Ser)]

NM_017662.5(TRPM6):c.499G>T (p.Ala167Ser)

Gene:
TRPM6:transient receptor potential cation channel subfamily M member 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q21.13
Genomic location:
Preferred name:
NM_017662.5(TRPM6):c.499G>T (p.Ala167Ser)
HGVS:
  • NC_000009.12:g.74840069C>A
  • NG_017036.1:g.53026G>T
  • NM_001177310.2:c.484G>T
  • NM_001177311.2:c.484G>T
  • NM_017662.5:c.499G>TMANE SELECT
  • NP_001170781.1:p.Ala162Ser
  • NP_001170782.1:p.Ala162Ser
  • NP_060132.3:p.Ala167Ser
  • NC_000009.11:g.77454985C>A
  • NM_017662.4:c.499G>T
Protein change:
A162S
Links:
dbSNP: rs141014694
NCBI 1000 Genomes Browser:
rs141014694
Molecular consequence:
  • NM_001177310.2:c.484G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177311.2:c.484G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_017662.5:c.499G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000779818GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(May 15, 2018) 		germlineclinical testing

Citation Link,

SCV002377675Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely benign
(Dec 19, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot 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 GeneDx, SCV000779818.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The A167S variant in the TRPM6 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A167S variant is observed in 40/10,150 (0.39%) alleles from individuals of Ashkenazi Jewish background in large population cohorts (Lek et al., 2016). The A167S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. We interpret A167S as a variant of uncertain significance.

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002377675.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024