ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.3255C>T (p.Asp1085=)

gnomAD frequency: 0.00048  dbSNP: rs368625295
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000513275 SCV000608971 uncertain significance not provided 2017-05-01 criteria provided, single submitter clinical testing
GeneDx RCV000513275 SCV000983643 likely benign not provided 2018-04-13 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001068538 SCV001233655 uncertain significance Nemaline myopathy 2 2022-08-02 criteria provided, single submitter clinical testing This sequence change affects codon 1085 of the NEB mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NEB protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs368625295, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 444522). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV001068538 SCV002557468 uncertain significance Nemaline myopathy 2 2020-05-21 criteria provided, single submitter clinical testing A heterozygous synonymous variant was identified, NM_001271208.1(NEB):c.3255C>T in exon 32 of 183 of the NEB gene. While this substitution does not change an amino acid, it may create a splice site change leading to aberrant splicing. Further testing via RNA studies are required to confirm if splicing is altered. The nucleotide at this position has low conservation (PhyloP, UCSC). In silico software does not predict the splice site variant to cause aberrant splicing (NetGene2, Fruit fly, Human Splicing Finder). The variant is present in the gnomAD population database at a frequency of 0.018% (49 heterozygotes, 0 homozygotes). Within the African subpopulation, the variant has a frequency of 0.125% (30 heterozygotes, 0 homozygotes). It has been previously reported as a VUS (ClinVar). Based on information available at the time of curation, this variant has been classified as a VARIANT of UNKNOWN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE.
Revvity Omics, Revvity RCV000513275 SCV003812184 uncertain significance not provided 2023-12-29 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004551647 SCV004766571 likely benign NEB-related disorder 2024-09-08 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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