rs397514352
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM2PM5PP3_StrongPP5_Moderate
The NM_001370658.1(BTD):c.274G>A(p.Glu92Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,016 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E92Q) has been classified as Pathogenic.
Frequency
Consequence
NM_001370658.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BTD | NM_001370658.1 | c.274G>A | p.Glu92Lys | missense_variant | 3/4 | ENST00000643237.3 | NP_001357587.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BTD | ENST00000643237.3 | c.274G>A | p.Glu92Lys | missense_variant | 3/4 | NM_001370658.1 | ENSP00000495254 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250318Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135256
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461016Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726746
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Biotinidase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 19, 2023 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu112 amino acid residue in BTD. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9396567). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 14707518). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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 sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 112 of the BTD protein (p.Glu112Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at