chr16-2496587-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate
The NM_001199107.2(TBC1D24):c.439G>C(p.Asp147His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,194 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. D147N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001199107.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBC1D24 | NM_001199107.2 | c.439G>C | p.Asp147His | missense_variant | 2/8 | ENST00000646147.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBC1D24 | ENST00000646147.1 | c.439G>C | p.Asp147His | missense_variant | 2/8 | NM_001199107.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000408 AC: 1AN: 244966Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133674
GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457194Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725174
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial infantile myoclonic epilepsy Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | Division of Medical Genetics; Sainte-Justine Hospital | Dec 22, 2014 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 10, 2010 | - - |
Developmental and epileptic encephalopathy, 1;C3892048:Autosomal dominant nonsyndromic hearing loss 65;CN236805:Caused by mutation in the TBC1 domain family, member 24 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 04, 2022 | This variant is present in population databases (rs267607103, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects TBC1D24 function (PMID: 20727515). 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 TBC1D24 protein function. ClinVar contains an entry for this variant (Variation ID: 48). This missense change has been observed in individual(s) with autosomal recessive familial infantile myoclonic epilepsy (PMID: 20727515). It has also been observed to segregate with disease in related individuals. This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 147 of the TBC1D24 protein (p.Asp147His). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at