19-48796622-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001190.4(BCAT2):c.1021G>A(p.Ala341Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,516 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 (★).
Frequency
Consequence
NM_001190.4 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCAT2 | NM_001190.4 | c.1021G>A | p.Ala341Thr | missense_variant | Exon 9 of 11 | ENST00000316273.11 | NP_001181.2 | |
BCAT2 | NM_001284325.2 | c.901G>A | p.Ala301Thr | missense_variant | Exon 10 of 12 | NP_001271254.1 | ||
BCAT2 | NM_001164773.2 | c.745G>A | p.Ala249Thr | missense_variant | Exon 7 of 9 | NP_001158245.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 250504Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135554
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461358Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13AN XY: 727040
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74322
ClinVar
Submissions by phenotype
Hypervalinemia and hyperleucine-isoleucinemia Pathogenic:1
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not provided Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with branched-chain amino acid transferase 2 deficiency (PMID: 31177572). This variant is present in population databases (rs779570956, gnomAD 0.006%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 341 of the BCAT2 protein (p.Ala341Thr). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at