Submissions for variant NM_015102.5(NPHP4):c.944C>T (p.Thr315Met)

gnomAD frequency: 0.00033  dbSNP: rs200684272

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000593942	SCV000706232	likely benign	not specified	2017-02-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000866112	SCV001007163	benign	Nephronophthisis	2025-01-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003409867	SCV004128053	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	NPHP4: BS2
Breakthrough Genomics, Breakthrough Genomics	RCV003409867	SCV005258228	likely benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000593942	SCV001548756	benign	not specified		no assertion criteria provided	clinical testing	The NPHP4 p.T315M variant was not identified in the literature but was identified in dbSNP (ID: rs200684272) and ClinVar (classified as benign by Invitae and as likely benign by EGL Genetic Diagnostics). The variant was identified in control databases in 297 of 280526 chromosomes (5 homozygous) at a frequency of 0.001059, and was observed at the highest frequency in the South Asian population in 214 of 30590 chromosomes (5 homozygous) (freq: 0.006996) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.T315 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
PreventionGenetics, part of Exact Sciences	RCV004543364	SCV004766911	likely benign	NPHP4-related disorder	2020-01-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).