chr6-80106698-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_183050.4(BCKDHB):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,555,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.
Frequency
Consequence
NM_183050.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCKDHB | NM_183050.4 | c.5C>T | p.Ala2Val | missense_variant | 1/10 | ENST00000320393.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCKDHB | ENST00000320393.9 | c.5C>T | p.Ala2Val | missense_variant | 1/10 | 1 | NM_183050.4 | P1 | |
BCKDHB | ENST00000356489.9 | c.5C>T | p.Ala2Val | missense_variant | 1/11 | 1 | P1 | ||
BCKDHB | ENST00000369760.8 | c.5C>T | p.Ala2Val | missense_variant | 1/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000257 AC: 4AN: 155356Hom.: 0 AF XY: 0.0000240 AC XY: 2AN XY: 83446
GnomAD4 exome AF: 0.0000171 AC: 24AN: 1403258Hom.: 0 Cov.: 32 AF XY: 0.0000101 AC XY: 7AN XY: 692762
GnomAD4 genome AF: 0.000118 AC: 18AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000942 AC XY: 7AN XY: 74322
ClinVar
Submissions by phenotype
Maple syrup urine disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 19, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the BCKDHB protein (p.Ala2Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with BCKDHB-related conditions. ClinVar contains an entry for this variant (Variation ID: 968447). 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: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. - |
Maple syrup urine disease type 1B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 21, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at