rs575173753
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_001199107.2(TBC1D24):āc.90T>Cā(p.Thr30=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,934 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 33)
Exomes š: 0.000055 ( 1 hom. )
Consequence
TBC1D24
NM_001199107.2 synonymous
NM_001199107.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.51
Genes affected
TBC1D24 (HGNC:29203): (TBC1 domain family member 24) This gene encodes a protein with a conserved domain, referred to as the TBC domain, characteristic of proteins which interact with GTPases. TBC domain proteins may serve as GTPase-activating proteins for a particular group of GTPases, the Rab (Ras-related proteins in brain) small GTPases which are involved in the regulation of membrane trafficking. Mutations in this gene are associated with familial infantile myoclonic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-1.07).
BP6
?
Variant 16-2496238-T-C is Benign according to our data. Variant chr16-2496238-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 227985.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=3}.
BP7
?
Synonymous conserved (PhyloP=-4.51 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000554 (81/1461578) while in subpopulation EAS AF= 0.00186 (74/39700). AF 95% confidence interval is 0.00152. There are 1 homozygotes in gnomad4_exome. There are 43 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBC1D24 | NM_001199107.2 | c.90T>C | p.Thr30= | synonymous_variant | 2/8 | ENST00000646147.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBC1D24 | ENST00000646147.1 | c.90T>C | p.Thr30= | synonymous_variant | 2/8 | NM_001199107.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152238Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000136 AC: 34AN: 249376Hom.: 0 AF XY: 0.0000887 AC XY: 12AN XY: 135356
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GnomAD4 exome AF: 0.0000554 AC: 81AN: 1461578Hom.: 1 Cov.: 31 AF XY: 0.0000591 AC XY: 43AN XY: 727104
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GnomAD4 genome ? AF: 0.0000459 AC: 7AN: 152356Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74508
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Familial infantile myoclonic epilepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | p.Thr30Thr in exon 2 of TBC1D24: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.1% (8/8588) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs575173753). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 11, 2021 | - - |
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 | Invitae | Sep 19, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at