ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.734C>T (p.Thr245Met)

gnomAD frequency: 0.00009  dbSNP: rs142608957
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000338911 SCV000340495 uncertain significance not provided 2016-03-16 criteria provided, single submitter clinical testing
GeneDx RCV000338911 SCV001792666 uncertain significance not provided 2021-03-29 criteria provided, single submitter clinical testing Observed in a fetus evaluated for prenatal hypophosphatasia; however, the patient's postnatal findings were consistent with OI and a homozygous variant in the CRTAP gene was identified (Sperelakis-Beedham et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32973344, 33549410)
Fulgent Genetics, Fulgent Genetics RCV002487243 SCV002784699 uncertain significance Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2021-10-13 criteria provided, single submitter clinical testing
Invitae RCV000338911 SCV003257258 uncertain significance not provided 2023-12-03 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 245 of the ALPL protein (p.Thr245Met). This variant is present in population databases (rs142608957, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALPL-related conditions. ClinVar contains an entry for this variant (Variation ID: 286903). 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 expected to disrupt ALPL protein function with a positive 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.
Natera, Inc. RCV001828236 SCV002094069 uncertain significance Hypophosphatasia 2019-10-28 no assertion criteria provided clinical testing

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