Submissions for variant NM_031407.7(HUWE1):c.5108C>T (p.Thr1703Met)

gnomAD frequency: 0.00005  dbSNP: rs1047233939

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002308522	SCV002600316	likely benign	not specified	2024-04-23	criteria provided, single submitter	clinical testing	Variant summary: HUWE1 c.5108C>T (p.Thr1703Met) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.5e-05 in 1204074 control chromosomes, including 7 hemizygotes (gnomAD 4.0.0) suggesting a benign role for the variant. To our knowledge, no occurrence of c.5108C>T in individuals affected with Intellectual Disability, X-Linked Syndromic, Turner Type and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1723246). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004534047	SCV004114525	uncertain significance	HUWE1-related disorder	2023-07-10	criteria provided, single submitter	clinical testing	The HUWE1 c.5108C>T variant is predicted to result in the amino acid substitution p.Thr1703Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-53611199-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.