NM_000071.3(CBS):c.179C>T (p.Ala60Val) AND HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 21, 2022
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:: RCV002241981.5

Allele description [Variation Report for NM_000071.3(CBS):c.179C>T (p.Ala60Val)]

NM_000071.3(CBS):c.179C>T (p.Ala60Val)

Gene:

CBS:cystathionine beta-synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.3

Genomic location:

Preferred name:

NM_000071.3(CBS):c.179C>T (p.Ala60Val)

HGVS:

NC_000021.9:g.43072015G>A
NG_008938.1:g.8916C>T
NM_000071.3:c.179C>TMANE SELECT
NM_001178008.3:c.179C>T
NM_001178009.3:c.179C>T
NM_001320298.2:c.179C>T
NP_000062.1:p.Ala60Val
NP_001171479.1:p.Ala60Val
NP_001171480.1:p.Ala60Val
NP_001307227.1:p.Ala60Val
LRG_777:g.8916C>T
NC_000021.8:g.44492125G>A

Protein change:

A60V

Links:

dbSNP: rs765352771

NCBI 1000 Genomes Browser:

rs765352771

Molecular consequence:

NM_000071.3:c.179C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178008.3:c.179C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001178009.3:c.179C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320298.2:c.179C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED
Identifiers:: MedGen: C3150344

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Metalasia divergens subsp. divergens voucher Karis 930 internal transcribed spac...
Metalasia divergens subsp. divergens voucher Karis 930 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|338856777|gb|JF893856.1|

Nucleotide
Metalasia rhoderoides voucher Karis 147 internal transcribed spacer 1, partial s...
Metalasia rhoderoides voucher Karis 147 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|338856787|gb|JF893866.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001508193	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001508193

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 21, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001508193.3

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 60 of the CBS protein (p.Ala60Val). This variant is present in population databases (rs765352771, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with CBS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1018254). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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

Last Updated: Sep 29, 2024

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