Submissions for variant NM_001008537.3(NEXMIF):c.1441C>T (p.Arg481Ter)

dbSNP: rs886041701

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000361637	SCV000330432	pathogenic	not provided	2023-01-30	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; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27568816, 27358180, 33144681, 31175295, 35032046)
Ambry Genetics	RCV000624677	SCV000740833	pathogenic	Inborn genetic diseases	2020-09-30	criteria provided, single submitter	clinical testing	The c.1441C>T (p.R481*) alteration, located in exon 3 (coding exon 2) of the KIAA2022 gene, consists of a C to T substitution at nucleotide position 1441. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 481. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. In one study, this mutation was detected in a nonverbal, nonambulatory female who also had intellectual disability, microcephaly, dysmorphic features, and hypotonia (de Lange, 2016). In our internal cohort, this variant occurred de novo in two females; one individual presented with epilepsy while the other presented with hypotonia, developmental delay, and dysmorphic features (Ambry internal data). Based on the available evidence, this alteration is classified as pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000361637	SCV001247745	pathogenic	not provided	2019-07-01	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000505390	SCV002018297	pathogenic	X-linked intellectual disability, Cantagrel type	2021-11-09	criteria provided, single submitter	clinical testing
Invitae	RCV000361637	SCV002245801	pathogenic	not provided	2023-12-07	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg481*) in the NEXMIF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NEXMIF are known to be pathogenic (PMID: 23615299). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of NEXMIF-related conditions (PMID: 27358180). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 280509). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000505390	SCV002526693	pathogenic	X-linked intellectual disability, Cantagrel type	2022-05-11	criteria provided, single submitter	clinical testing	This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PVS1, PS2_MOD, PS4_MOD, PM2_SUP
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000505390	SCV002586413	pathogenic	X-linked intellectual disability, Cantagrel type		criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000505390	SCV002759356	pathogenic	X-linked intellectual disability, Cantagrel type	2022-12-07	criteria provided, single submitter	clinical testing
OMIM	RCV000505390	SCV000599601	pathogenic	X-linked intellectual disability, Cantagrel type	2021-08-20	no assertion criteria provided	literature only