ClinVar Miner

Submissions for variant NM_182961.4(SYNE1):c.11999C>A (p.Ala4000Glu)

gnomAD frequency: 0.00006  dbSNP: rs375752705
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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 RCV000804644 SCV000944561 uncertain significance Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 3929 of the SYNE1 protein (p.Ala3929Glu). This variant is present in population databases (rs375752705, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SYNE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 649662). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Athena Diagnostics RCV002473145 SCV002771379 uncertain significance not provided 2021-08-19 criteria provided, single submitter clinical testing
GeneDx RCV002473145 SCV005379650 uncertain significance not provided 2023-12-03 criteria provided, single submitter clinical testing Reported as a single heterozygous variant in an individual with autism who also harbored variants in several other genes that may be related to the phenotype (PMID: 34368859); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34368859)

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