Submissions for variant NM_001195518.2(MICU1):c.1072-1G>C

dbSNP: rs754639936

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001818255	SCV002064137	pathogenic	not provided	2022-01-20	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24336167, 28132899)
Lifecell International Pvt. Ltd	RCV000087303	SCV003853256	pathogenic	Proximal myopathy with extrapyramidal signs		criteria provided, single submitter	clinical testing	A Heterozygous Intron, Splice site acceptor variant c.1078-1G>C in Exon 10 of the MICU1 gene that results in the amino acid substitution was identified. The observed variant has a minor allele frequency of 0.00005% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic (variant id: 101045). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.
Neuberg Centre For Genomic Medicine, NCGM	RCV000087303	SCV004047423	pathogenic	Proximal myopathy with extrapyramidal signs		criteria provided, single submitter	clinical testing	The splice site variant c.1072-1G>C has been reported previously in affected individuals (Logan CV et.al.,2014). This variant has been reported to the ClinVar database as Pathogenic. The c.1072-1G>C variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.005250% is reported in gnomAD. The variant affects an invariant splice nucleotide and is expected to cause loss of function. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic
OMIM	RCV000087303	SCV000120181	pathogenic	Proximal myopathy with extrapyramidal signs	2014-02-01	no assertion criteria provided	literature only