Submissions for variant NM_001164508.2(NEB):c.10338T>C (p.Asn3446=)

gnomAD frequency: 0.00870  dbSNP: rs147569843

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000247721	SCV000307183	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000247721	SCV000528497	benign	not specified	2016-07-08	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.
Athena Diagnostics	RCV000586906	SCV000614159	benign	not provided	2019-06-27	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082593	SCV000640476	benign	Nemaline myopathy 2	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586906	SCV000697796	benign	not provided	2017-04-24	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.10338T>C (p.Asn3446Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts the creation of SRp40 binding site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 926/120706 control chromosomes (19 homozygotes) from ExAC at a frequency of 0.0076715, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this variant is likely a benign polymorphism. The variant is more common in East Asian population with allele frequency of 5.4% (465/8592 chromosomes). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001082593	SCV001294685	benign	Nemaline myopathy 2	2018-04-20	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Breakthrough Genomics, Breakthrough Genomics	RCV000586906	SCV005238895	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001082593	SCV002077123	benign	Nemaline myopathy 2	2020-09-16	no assertion criteria provided	clinical testing