Submissions for variant NM_005921.2(MAP3K1):c.4258-5T>C

gnomAD frequency: 0.00001  dbSNP: rs761483754

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000704922	SCV000833895	uncertain significance	46,XY sex reversal 6	2018-04-17	criteria provided, single submitter	clinical testing	This sequence change falls in intron 18 of the MAP3K1 gene. It does not directly change the encoded amino acid sequence of the MAP3K1 protein. This variant is present in population databases (rs761483754, ExAC 0.009%). This variant has not been reported in the literature in individuals with MAP3K1-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, 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.
PreventionGenetics, part of Exact Sciences	RCV003965452	SCV004782626	likely benign	MAP3K1-related disorder	2019-08-21	criteria provided, single submitter	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).