NM_000071.3(CBS):c.457G>A (p.Gly153Arg) AND Homocystinuria

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 9, 2017
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:: RCV000781198.3

Allele description [Variation Report for NM_000071.3(CBS):c.457G>A (p.Gly153Arg)]

NM_000071.3(CBS):c.457G>A (p.Gly153Arg)

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.457G>A (p.Gly153Arg)

HGVS:

NC_000021.9:g.43065690C>T
NG_008938.1:g.15241G>A
NM_000071.3:c.457G>AMANE SELECT
NM_001178008.3:c.457G>A
NM_001178009.3:c.457G>A
NM_001320298.2:c.457G>A
NM_001321072.1:c.142G>A
NP_000062.1:p.Gly153Arg
NP_000062.1:p.Gly153Arg
NP_001171479.1:p.Gly153Arg
NP_001171480.1:p.Gly153Arg
NP_001307227.1:p.Gly153Arg
NP_001308001.1:p.Gly48Arg
LRG_777t1:c.457G>A
LRG_777:g.15241G>A
LRG_777p1:p.Gly153Arg
NC_000021.8:g.44485800C>T
NM_000071.2:c.457G>A

Protein change:

G153R

Links:

dbSNP: rs745704046

NCBI 1000 Genomes Browser:

rs745704046

Molecular consequence:

NM_000071.3:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178008.3:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178009.3:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320298.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001321072.1:c.142G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Homocystinuria
Identifiers:: MONDO: MONDO:0004737; MedGen: C0019880; Human Phenotype Ontology: HP:0002156

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000919083	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Nov 9, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22267502, 20455263, 21517828 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000919083

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Nov 9, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Surrogate genetics and metabolic profiling for characterization of human disease alleles.

Mayfield JA, Davies MW, Dimster-Denk D, Pleskac N, McCarthy S, Boydston EA, Fink L, Lin XX, Narain AS, Meighan M, Rine J.

Genetics. 2012 Apr;190(4):1309-23. doi: 10.1534/genetics.111.137471. Epub 2012 Jan 20. Erratum in: Genetics. 2012 Oct;192(2):759-60.

PubMed [citation]

PMID:: 22267502
PMCID:: PMC3316645

Testing computational prediction of missense mutation phenotypes: functional characterization of 204 mutations of human cystathionine beta synthase.

Wei Q, Wang L, Wang Q, Kruger WD, Dunbrack RL Jr.

Proteins. 2010 Jul;78(9):2058-74. doi: 10.1002/prot.22722.

PubMed [citation]

PMID:: 20455263
PMCID:: PMC3040297

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919083.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: The CBS c.457G>A (p.Gly153Arg) variant involves the alteration of a conserved nucleotide that lies within the pyridoxal-phosphate dependent enzyme domain (InterPro). 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 1/156632 control chromosomes at a frequency of 0.0000064, which does not exceed the estimated maximal expected allele frequency of a pathogenic CBS variant (0.0030414). The variant has been reported in a Saudi Arabian family, where two affected patients were homozygous for the variant, which was inherited from unaffected consanguineous heterozygous parents (Zaidi_2012). Additionally, two functional studies in yeast suggest that the variant may impact protein function (Wei_2010, Mayfield_2012). Taken together, this variant is classified as likely pathogenic.

#	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: Oct 8, 2024

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