Submissions for variant NM_015909.4(NBAS):c.4300G>A (p.Asp1434Asn)

dbSNP: rs750091340

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Fulgent Genetics, Fulgent Genetics	RCV002496021	SCV002784803	uncertain significance	Short stature-optic atrophy-Pelger-HuC+t anomaly syndrome; Infantile liver failure syndrome 2	2022-03-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001699739	SCV003328805	uncertain significance	not provided	2023-11-12	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1434 of the NBAS protein (p.Asp1434Asn). This variant is present in population databases (rs750091340, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with NBAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1284517). 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 NBAS protein function with a negative predictive value of 80%. 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.
Clinical Genetics, Academic Medical Center	RCV001699739	SCV001918167	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699739	SCV001952254	uncertain significance	not provided		no assertion criteria provided	clinical testing