3-15645093-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001370658.1(BTD):c.1177G>C(p.Gly393Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,192 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_001370658.1 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 |
---|---|---|---|---|---|---|---|---|
BTD | NM_001370658.1 | c.1177G>C | p.Gly393Arg | missense_variant | Exon 4 of 4 | ENST00000643237.3 | NP_001357587.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152192Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Biotinidase deficiency Uncertain:1
This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 413 of the BTD protein (p.Gly413Arg). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with biochemical features of biotinidase deficiency (Invitae). ClinVar contains an entry for this variant (Variation ID: 2113926). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BTD protein function. 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