ClinVar Miner

Submissions for variant NM_001080517.3(SETD5):c.3856del (p.Ser1286fs)

dbSNP: rs587777329
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623440 SCV000741923 uncertain significance Inborn genetic diseases 2017-10-06 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268332 SCV001447173 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneDx RCV001268332 SCV001875136 pathogenic not provided 2022-04-21 criteria provided, single submitter clinical testing Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 157 amino acids are lost and replaced with 83 incorrect amino acids; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24680889)
DASA RCV000114964 SCV002097274 likely pathogenic Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency 2022-02-14 criteria provided, single submitter clinical testing The c.3562del;p.(Ser1188Leufs*84) is a null frameshift variant in the SETD5 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript -PVS1_strong. This variant is not present in population databases (rs587777329, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001268332 SCV004292200 pathogenic not provided 2024-08-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1286Leufs*84) in the SETD5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 157 amino acid(s) of the SETD5 protein. This variant is present in population databases (no rsID available, gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with severe intellectual disability (PMID: 24680889). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 127106). This variant disrupts a region of the SETD5 protein in which other variant(s) (p.Ser1286Leufs*37) have been determined to be pathogenic (PMID: 28549204; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000114964 SCV000148874 pathogenic Intellectual disability-facial dysmorphism syndrome due to SETD5 haploinsufficiency 2014-04-03 no assertion criteria provided literature only

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