ClinVar Miner

Submissions for variant NM_001199107.2(TBC1D24):c.485A>G (p.Asn162Ser)

gnomAD frequency: 0.00002  dbSNP: rs772054145
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000602701 SCV000713706 uncertain significance not specified 2017-09-28 criteria provided, single submitter clinical testing The p.Asn162Ser variant in TBC1D24 has not been previously reported in individua ls with hearing loss, nonsyndromic epilepsy, or DOORS syndrome, but has been ide ntified in 0.01% (4/33566) of Latino chromosomes by the Genome Aggregation Datab ase (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs772054145). Although this variant has been seen in the general population, its frequency is not high enou gh to rule out a pathogenic role. Computational prediction tools and conservatio n analysis do not provide strong support for or against an impact to the protein . In summary, the clinical significance of the p.Asn162Ser variant is uncertain. ACMG/AMP Criteria applied: PM2 supporting (Richards 2015).
Invitae RCV000796640 SCV000936161 uncertain significance Developmental and epileptic encephalopathy, 1; Autosomal dominant nonsyndromic hearing loss 65; Caused by mutation in the TBC1 domain family, member 24 2023-01-17 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt TBC1D24 protein function. ClinVar contains an entry for this variant (Variation ID: 506170). This variant has not been reported in the literature in individuals affected with TBC1D24-related conditions. This variant is present in population databases (rs772054145, gnomAD 0.01%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 162 of the TBC1D24 protein (p.Asn162Ser).
Athena Diagnostics Inc RCV000993242 SCV001146069 uncertain significance not provided 2018-11-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV002529356 SCV003625579 uncertain significance Inborn genetic diseases 2022-06-10 criteria provided, single submitter clinical testing The c.485A>G (p.N162S) alteration is located in exon 2 (coding exon 1) of the TBC1D24 gene. This alteration results from a A to G substitution at nucleotide position 485, causing the asparagine (N) at amino acid position 162 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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