rs112029370
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM1PP2BP4_Moderate
The NM_000071.3(CBS):c.296T>C(p.Phe99Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F99Y) has been classified as Likely benign.
Frequency
Consequence
NM_000071.3 missense
Scores
Clinical Significance
Conservation
Publications
- classic homocystinuriaInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, PanelApp Australia, ClinGen, Genomics England PanelApp
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000257 AC: 1AN: 38986Hom.: 0 Cov.: 6 show subpopulations
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000293 AC: 1AN: 340968Hom.: 0 Cov.: 0 AF XY: 0.00000545 AC XY: 1AN XY: 183546 show subpopulations
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000512 AC: 2AN: 39074Hom.: 0 Cov.: 6 AF XY: 0.0000556 AC XY: 1AN XY: 17998 show subpopulations
ClinVar
Submissions by phenotype
HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED Uncertain:1
This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 99 of the CBS protein (p.Phe99Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CBS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at