chr2-43831957-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate
The NM_022436.3(ABCG5):āc.392A>Gā(p.Tyr131Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000458 in 1,550,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y131H) has been classified as Uncertain significance.
Frequency
Consequence
NM_022436.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ABCG5 | NM_022436.3 | c.392A>G | p.Tyr131Cys | missense_variant | 3/13 | ENST00000405322.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ABCG5 | ENST00000405322.8 | c.392A>G | p.Tyr131Cys | missense_variant | 3/13 | 1 | NM_022436.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151936Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000921 AC: 14AN: 152038Hom.: 0 AF XY: 0.000123 AC XY: 10AN XY: 81388
GnomAD4 exome AF: 0.0000458 AC: 64AN: 1397962Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 37AN XY: 689498
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152054Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74336
ClinVar
Submissions by phenotype
Sitosterolemia 2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 21, 2022 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 11, 2017 | - - |
Sitosterolemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 03, 2024 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 131 of the ABCG5 protein (p.Tyr131Cys). This variant is present in population databases (rs569748582, gnomAD 0.03%). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 32088153). ClinVar contains an entry for this variant (Variation ID: 594497). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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