rs370163789
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_000071.3(CBS):āc.1067T>Cā(p.Val356Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. V356V) has been classified as Likely benign.
Frequency
Consequence
NM_000071.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBS | NM_000071.3 | c.1067T>C | p.Val356Ala | missense_variant | 12/17 | ENST00000398165.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBS | ENST00000398165.8 | c.1067T>C | p.Val356Ala | missense_variant | 12/17 | 1 | NM_000071.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 0
GnomAD3 exomes AF: 0.00000419 AC: 1AN: 238714Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131000
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 43102Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 22962
GnomAD4 genome Cov.: 0
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2016 | The p.V356A variant (also known as c.1067T>C), located in coding exon 10 of the CBS gene, results from a T to C substitution at nucleotide position 1067. The valine at codon 356 is replaced by alanine, an amino acid with similar properties. This variant was included in a study of CBS alterations' B6 cofactor sensitivity and was reported as having no significant differences versus wild-type in yeast culture growth rate at increasing pyridoxine concentrations (Dimster-Denk D et al. G3 (Bethesda), 2013 Oct;3:1619-28). This amino acid position is not well conserved in available vertebrate species, and alanine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Classic homocystinuria Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at