ClinVar Miner

Submissions for variant NM_001378454.1(ALMS1):c.11764A>G (p.Asn3922Asp)

gnomAD frequency: 0.00001  dbSNP: rs45486496
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489738 SCV000576991 uncertain significance not provided 2018-12-31 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALMS1 gene. The N3923D variant has not been published as pathogenic or been reported as benign to our knowledge. N3923D has been observed in 38/30780 (0.12%) alleles from individuals of South Asian ancestry in large population cohorts, though no individuals were reported to be homozygous (Lek et al., 2016). The N3923D variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Lastly, while some missense variants have been reported in association with Alstrom syndrome, most pathogenic variants in ALMS1 reported to date are predicted to cause premature protein truncation (Marshall et al., 2012; Stenson et al., 2014).
Invitae RCV001272757 SCV003462028 uncertain significance Alstrom syndrome 2022-07-22 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 3923 of the ALMS1 protein (p.Asn3923Asp). This variant is present in population databases (rs45486496, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 426526). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. RCV001272757 SCV001455028 uncertain significance Alstrom syndrome 2020-09-16 no assertion criteria provided clinical testing

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