ClinVar Miner

Submissions for variant NM_002700.3(POU4F3):c.214C>G (p.His72Asp)

gnomAD frequency: 0.00009  dbSNP: rs370712489
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000659028 SCV000780832 uncertain significance not provided 2023-01-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001152219 SCV001313429 uncertain significance Autosomal dominant nonsyndromic hearing loss 15 2018-01-13 criteria provided, single submitter clinical testing 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.
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375280 SCV001571806 likely benign Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing BS2_Strong, BP4_Supporting
GeneDx RCV000659028 SCV001787434 uncertain significance not provided 2023-07-17 criteria provided, single submitter clinical testing 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
Invitae RCV000659028 SCV003300542 uncertain significance not provided 2022-11-21 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 POU4F3 protein function. ClinVar contains an entry for this variant (Variation ID: 546983). This variant has not been reported in the literature in individuals affected with POU4F3-related conditions. This variant is present in population databases (rs370712489, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 72 of the POU4F3 protein (p.His72Asp).
Ambry Genetics RCV003163034 SCV003889047 uncertain significance Inborn genetic diseases 2023-02-28 criteria provided, single submitter clinical testing The c.214C>G (p.H72D) alteration is located in exon 2 (coding exon 2) of the POU4F3 gene. This alteration results from a C to G substitution at nucleotide position 214, causing the histidine (H) at amino acid position 72 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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