1-179557179-G-T

Variant names:

• chr1-179557179-G-T
• rs12568913
• NM_014625.4:c.586C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014625.4(NPHS2):​c.586C>A​(p.Arg196Arg) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPHS2 NM_014625.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82
• Publications: 2 publications found

Genes affected

NPHS2 (HGNC:13394): (NPHS2 stomatin family member, podocin) This gene encodes a protein that plays a role in the regulation of glomerular permeability. Mutations in this gene cause steroid-resistant nephrotic syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

NPHS2 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Ambry Genetics, G2P
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHS2	NM_014625.4	MANE Select	c.586C>A	p.Arg196Arg	synonymous	Exon 5 of 8	NP_055440.1	Q9NP85-1
	NPHS2	NM_001297575.2		c.534+2500C>A		intron	N/A	NP_001284504.1	Q9NP85-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHS2	ENST00000367615.9	TSL:1 MANE Select	c.586C>A	p.Arg196Arg	synonymous	Exon 5 of 8	ENSP00000356587.4	Q9NP85-1
	NPHS2	ENST00000367616.4	TSL:1	c.534+2500C>A		intron	N/A	ENSP00000356588.4	Q9NP85-2
	NPHS2	ENST00000902256.1		c.409C>A	p.Arg137Arg	synonymous	Exon 3 of 6	ENSP00000572315.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	10
DANN	Benign	0.73
PhyloP100		3.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12568913; hg19: chr1-179526314;