Submissions for variant NM_007126.5(VCP):c.1194+3G>A

gnomAD frequency: 0.00008  dbSNP: rs183223259

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000685579	SCV000813064	uncertain significance	Frontotemporal dementia and/or amyotrophic lateral sclerosis 6; Inclusion body myopathy with Paget disease of bone and frontotemporal dementia	2024-01-26	criteria provided, single submitter	clinical testing	This sequence change falls in intron 10 of the VCP gene. It does not directly change the encoded amino acid sequence of the VCP protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs183223259, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has been observed in individual(s) with amyotrophic lateral sclerosis with frontotemporal dementia (PMID: 27790088). ClinVar contains an entry for this variant (Variation ID: 565903). Variants that disrupt 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. 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.
Eurofins Ntd Llc (ga)	RCV000733640	SCV000861730	uncertain significance	not provided	2018-06-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000733640	SCV002504333	likely benign	not provided	2019-03-18	criteria provided, single submitter	clinical testing	See Variant Classification Assertion Criteria.
Ambry Genetics	RCV002334250	SCV002644706	likely benign	Inborn genetic diseases	2019-10-01	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity	RCV000733640	SCV003820395	uncertain significance	not provided	2023-08-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003938036	SCV004749637	likely benign	VCP-related condition	2023-05-31	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).