Submissions for variant NM_001134673.4(NFIA):c.361C>T (p.Arg121Cys)

dbSNP: rs886039429

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000254980	SCV000321917	pathogenic	not provided	2022-12-13	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35018717, 31730271)
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003152700	SCV001985037	pathogenic	Brain malformations with or without urinary tract defects	2021-08-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002518754	SCV003623119	uncertain significance	Inborn genetic diseases	2022-06-27	criteria provided, single submitter	clinical testing	The c.496C>T (p.R166C) alteration is located in exon 3 (coding exon 3) of the NFIA gene. This alteration results from a C to T substitution at nucleotide position 496, causing the arginine (R) at amino acid position 166 to be replaced by a cysteine (C). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
3billion, Medical Genetics	RCV003152700	SCV003841838	likely pathogenic	Brain malformations with or without urinary tract defects	2023-02-23	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.71; 3Cnet: 0.99). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000265253). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV003152700	SCV004171592	likely pathogenic	Brain malformations with or without urinary tract defects	2023-11-24	no assertion criteria provided	clinical testing
Solve-RD Consortium	RCV003152700	SCV005091515	likely pathogenic	Brain malformations with or without urinary tract defects	2022-06-01	no assertion criteria provided	provider interpretation	Variant confirmed as disease-causing by referring clinical team