Submissions for variant NM_001099287.2(NIPAL4):c.247C>T (p.Arg83Ter)

dbSNP: rs199422216

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000436418	SCV000513262	pathogenic	not provided	2020-06-16	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26456858, 25525159, 31347739, 15317751)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004579514	SCV005062080	pathogenic	Lamellar ichthyosis	2024-03-13	criteria provided, single submitter	clinical testing	Variant summary: NIPAL4 c.247C>T (p.Arg83X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 3.6e-05 in 247508 control chromosomes. c.247C>T has been reported in the literature in multiple individuals affected with Lamellar Ichthyosis (Lefevre_2004). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 15317751). ClinVar contains an entry for this variant (Variation ID: 1729). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM	RCV000001799	SCV000021955	pathogenic	Autosomal recessive congenital ichthyosis 6	2004-10-15	no assertion criteria provided	literature only
Institute for Human Genetics, University Medical Center Freiburg	RCV000001799	SCV000930507	pathogenic	Autosomal recessive congenital ichthyosis 6	2019-05-16	no assertion criteria provided	clinical testing