rs12373107
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001199107.2(TBC1D24):c.1440G>A(p.Ser480Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,601,820 control chromosomes in the GnomAD database, including 874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.023 ( 70 hom., cov: 33)
Exomes 𝑓: 0.029 ( 804 hom. )
Consequence
TBC1D24
NM_001199107.2 synonymous
NM_001199107.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -6.62
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 16-2500405-G-A is Benign according to our data. Variant chr16-2500405-G-A is described in ClinVar as [Benign]. Clinvar id is 130536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2500405-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-6.62 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBC1D24 | NM_001199107.2 | c.1440G>A | p.Ser480Ser | synonymous_variant | 7/8 | ENST00000646147.1 | NP_001186036.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBC1D24 | ENST00000646147.1 | c.1440G>A | p.Ser480Ser | synonymous_variant | 7/8 | NM_001199107.2 | ENSP00000494678.1 | |||
ENSG00000260272 | ENST00000564543.1 | c.965+3292G>A | intron_variant | 2 | ENSP00000455547.1 |
Frequencies
GnomAD3 genomes AF: 0.0232 AC: 3532AN: 152148Hom.: 70 Cov.: 33
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GnomAD3 exomes AF: 0.0320 AC: 7039AN: 219852Hom.: 231 AF XY: 0.0305 AC XY: 3660AN XY: 120102
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GnomAD4 exome AF: 0.0289 AC: 41889AN: 1449554Hom.: 804 Cov.: 33 AF XY: 0.0289 AC XY: 20800AN XY: 720002
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GnomAD4 genome AF: 0.0232 AC: 3532AN: 152266Hom.: 70 Cov.: 33 AF XY: 0.0231 AC XY: 1721AN XY: 74450
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ClinVar
Significance: Benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 17, 2014 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 13, 2015 | p.Ser480Ser in exon 7 of TBC1D24: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 2.6% (222/8400) of European American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12373107). - |
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Familial infantile myoclonic epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
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
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at