ClinVar Miner

Submissions for variant NM_145207.3(AFG2A):c.436G>A (p.Val146Met)

gnomAD frequency: 0.00033  dbSNP: rs374771569
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000529905 SCV000655998 uncertain significance Microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome 2022-11-01 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 146 of the SPATA5 protein (p.Val146Met). This variant is present in population databases (rs374771569, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with SPATA5-related conditions. ClinVar contains an entry for this variant (Variation ID: 475731). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SPATA5 protein function. 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.
GeneDx RCV001569043 SCV001793025 uncertain significance not provided 2024-12-15 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002527916 SCV003734404 uncertain significance Inborn genetic diseases 2023-06-26 criteria provided, single submitter clinical testing The c.436G>A (p.V146M) alteration is located in exon 3 (coding exon 3) of the SPATA5 gene. This alteration results from a G to A substitution at nucleotide position 436, causing the valine (V) at amino acid position 146 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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