Submissions for variant NM_015922.3(NSDHL):c.529A>G (p.Ile177Val)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003254516	SCV003944786	uncertain significance	Inborn genetic diseases	2023-05-09	criteria provided, single submitter	clinical testing	The c.529A>G (p.I177V) alteration is located in exon 5 (coding exon 4) of the NSDHL gene. This alteration results from a A to G substitution at nucleotide position 529, causing the isoleucine (I) at amino acid position 177 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003324092	SCV004029152	uncertain significance	not specified	2023-07-17	criteria provided, single submitter	clinical testing	Variant summary: NSDHL c.529A>G (p.Ile177Val) results in a conservative amino acid change located in the 3-beta hydroxysteroid dehydrogenase/isomerase family (IPR002225) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.5e-06 in 183474 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.529A>G in individuals affected with NSDHL-Related Disorder and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV005047494	SCV005683050	uncertain significance	Child syndrome; CK syndrome	2024-03-04	criteria provided, single submitter	clinical testing