Submissions for variant NM_002528.7(NTHL1):c.354+4G>T

gnomAD frequency: 0.00004  dbSNP: rs771353497

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000813619	SCV000953986	likely benign	not provided	2024-12-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000813619	SCV000983427	likely benign	not provided	2018-04-17	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV001021121	SCV001182698	uncertain significance	Hereditary cancer-predisposing syndrome	2025-02-26	criteria provided, single submitter	clinical testing	The c.378+4G>T intronic variant results from a G to T substitution 4 nucleotides after coding exon 2 in the NTHL1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this variant remains unclear.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002465788	SCV002760814	likely benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000813619	SCV004222203	uncertain significance	not provided	2022-09-07	criteria provided, single submitter	clinical testing	To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00038 (10/26090 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect NTHL1 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.
PreventionGenetics, part of Exact Sciences	RCV003892739	SCV004713444	likely benign	NTHL1-related disorder	2022-02-03	no assertion criteria provided	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).