rs755880523
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001199107.2(TBC1D24):c.1529G>A(p.Gly510Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,768 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 (★★). Synonymous variant affecting the same amino acid position (i.e. G510G) has been classified as Likely benign.
Frequency
Consequence
NM_001199107.2 missense
Scores
Clinical Significance
Conservation
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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.1529G>A | p.Gly510Glu | missense_variant | 8/8 | ENST00000646147.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBC1D24 | ENST00000646147.1 | c.1529G>A | p.Gly510Glu | missense_variant | 8/8 | NM_001199107.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000421 AC: 1AN: 237488Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 130160
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1451768Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 722646
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 13, 2017 | Variant classified as Uncertain Significance - Favor Pathogenic. The p.Gly510Glu variant in TBC1D24 has now been reported in trans with a likely pathogenic TBC1 D24 variant in one individual with hearing loss (LMM data). It has been identifi ed in 1/52804 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs755880523). Computational prediction to ols and conservation analysis suggest that the p.Gly510Glu variant may impact th e protein, though this information is not predictive enough to determine pathoge nicity. In summary, while there is some suspicion for a pathogenic role, the cli nical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PM3, PP3. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 12, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at