3-15644499-C-T
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM1PM2PP3_StrongPP5_Very_Strong
The NM_001370658.1(BTD):c.583C>T(p.Leu195Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,050 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 (★★). Synonymous variant affecting the same amino acid position (i.e. L195L) has been classified as Likely benign.
Frequency
Consequence
NM_001370658.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BTD | NM_001370658.1 | c.583C>T | p.Leu195Phe | missense_variant | 4/4 | ENST00000643237.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BTD | ENST00000643237.3 | c.583C>T | p.Leu195Phe | missense_variant | 4/4 | NM_001370658.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251486Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135916
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727248
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74326
ClinVar
Submissions by phenotype
Biotinidase deficiency Pathogenic:5
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Jul 21, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 10, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 215 of the BTD protein (p.Leu215Phe). This variant is present in population databases (rs190386869, gnomAD 0.004%). This missense change has been observed in individual(s) with biotinidase deficiency (PMID: 9396567, 9506660, 17185019, 25174816, 26361991, 27207447). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 25031). 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. For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jun 21, 2016 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | Feb 22, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at