rs200226466
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4_StrongBP6
The NM_001199107.2(TBC1D24):c.179G>A(p.Arg60Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,613,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001199107.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBC1D24 | ENST00000646147.1 | c.179G>A | p.Arg60Gln | missense_variant | Exon 2 of 8 | NM_001199107.2 | ENSP00000494678.1 | |||
ENSG00000260272 | ENST00000564543.1 | c.179G>A | p.Arg60Gln | missense_variant | Exon 1 of 3 | 2 | ENSP00000455547.1 |
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000189 AC: 47AN: 248866Hom.: 0 AF XY: 0.000207 AC XY: 28AN XY: 135252
GnomAD4 exome AF: 0.000215 AC: 314AN: 1461256Hom.: 0 Cov.: 31 AF XY: 0.000227 AC XY: 165AN XY: 726968
GnomAD4 genome AF: 0.000308 AC: 47AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19AN XY: 74510
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | TBC1D24: PM2:Supporting, BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2021 | This variant is associated with the following publications: (PMID: 27281533) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 27, 2016 | - - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 17, 2015 | p.Arg60Gln in exon 2 of TBC1D24: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, bushbaby and shrew have a glutamine (Gln) at this position despite high ne arby amino acid conservation. In addition, computational prediction tools sugges t that the p.Arg60Gln variant may not impact the protein and the variant also be en identified in 0.03% (22/65926) of European chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200226466). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 06, 2024 | Variant summary: TBC1D24 c.179G>A (p.Arg60Gln) results in a conservative amino acid change located in the Rab-GAP-TBC domain (IPR000195) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00022 in 1613610 control chromosomes, predominantly at a frequency of 0.00028 within the Non-Finnish European subpopulation in the gnomAD database. c.179G>A has been reported in the literature in at least an individual affected with TBC1D24-Related Disorders (example: Balestrini_2016). This report, however, does not provide unequivocal conclusions about association of the variant with TBC1D24-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 27281533). ClinVar contains an entry for this variant (Variation ID: 207518). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Familial infantile myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2018 | The p.R60Q variant (also known as c.179G>A), located in coding exon 1 of the TBC1D24 gene, results from a G to A substitution at nucleotide position 179. The arginine at codon 60 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and glutamine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
TBC1D24-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 04, 2024 | The TBC1D24 c.179G>A variant is predicted to result in the amino acid substitution p.Arg60Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.039% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Developmental and epileptic encephalopathy, 1;C3892048:Autosomal dominant nonsyndromic hearing loss 65;CN236805:Caused by mutation in the TBC1 domain family, member 24 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 09, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at