ClinVar Miner

Submissions for variant NM_001281463.1(SMC1A):c.1188+4G>A (rs781824288)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000717728 SCV000848586 uncertain significance History of neurodevelopmental disorder 2016-12-23 criteria provided, single submitter clinical testing The c.1254+4G>A intronic variant results from a G to A substitution 4 nucleotides after coding exon 7 in the SMC1A gene. This nucleotide position is not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001301464 SCV001490634 uncertain significance Congenital muscular hypertrophy-cerebral syndrome 2020-09-08 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the SMC1A gene. It does not directly change the encoded amino acid sequence of the SMC1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs781824288, ExAC 0.01%). This variant has not been reported in the literature in individuals with SMC1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 588589). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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.
Baylor Genetics RCV001301464 SCV001527402 uncertain significance Congenital muscular hypertrophy-cerebral syndrome 2018-08-08 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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