ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.532G>A (p.Val178Met)

gnomAD frequency: 0.00007  dbSNP: rs376003129
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001304282 SCV001493556 uncertain significance Familial aplasia of the vermis 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 178 of the INPP5E protein (p.Val178Met). This variant is present in population databases (rs376003129, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. ClinVar contains an entry for this variant (Variation ID: 1007141). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt INPP5E protein function with a negative predictive value of 95%. 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.
Breakthrough Genomics, Breakthrough Genomics RCV004692455 SCV005190587 uncertain significance not provided criteria provided, single submitter not provided
Fulgent Genetics, Fulgent Genetics RCV005040152 SCV005680020 uncertain significance MORM syndrome; Joubert syndrome 1 2024-04-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004756209 SCV005354007 uncertain significance INPP5E-related disorder 2024-03-07 no assertion criteria provided clinical testing The INPP5E c.532G>A variant is predicted to result in the amino acid substitution p.Val178Met. This variant has been reported in an individual with Bardet–Biedl syndrome, who was also homozygous for a pathogenic variant in BBS2 gene (Manara et al. 2019. PubMed ID: 31196119). This variant is reported in 0.012% 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.

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