ClinVar Miner

Submissions for variant NM_019892.6(INPP5E):c.739G>T (p.Asp247Tyr)

gnomAD frequency: 0.00001  dbSNP: rs749897420
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001243825 SCV001417008 uncertain significance Familial aplasia of the vermis 2022-06-20 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. This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 247 of the INPP5E protein (p.Asp247Tyr). 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 INPP5E protein function. ClinVar contains an entry for this variant (Variation ID: 968640). This variant has not been reported in the literature in individuals affected with INPP5E-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database.
Ambry Genetics RCV002564073 SCV003600714 uncertain significance Inborn genetic diseases 2022-01-19 criteria provided, single submitter clinical testing The c.739G>T (p.D247Y) alteration is located in exon 1 (coding exon 1) of the INPP5E gene. This alteration results from a G to T substitution at nucleotide position 739, causing the aspartic acid (D) at amino acid position 247 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003393911 SCV004119032 uncertain significance INPP5E-related condition 2023-06-29 criteria provided, single submitter clinical testing The INPP5E c.739G>T variant is predicted to result in the amino acid substitution p.Asp247Tyr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.019% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-139333133-C-A). 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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