rs528833893

Variant names:

• chr1-179559745-CAAAA-C
• NM_014625.4:c.464_467delTTTT

Your query was ambiguous. Multiple possible variants found:

• chr1-179559745-CAAAA-C
• chr1-179559745-CAAAA-CAAA
• chr1-179559745-CAAAA-CAAAAA
• chr1-179559745-CAAAA-CAAAAAA

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_014625.4(NPHS2):​c.464_467delTTTT​(p.Phe155CysfsTer25) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000702 in 1,424,154 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: NPHS2 NM_014625.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.96

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHS2	NM_014625.4	c.464_467delTTTT	p.Phe155CysfsTer25	frameshift_variant	Exon 4 of 8	ENST00000367615.9	NP_055440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPHS2	ENST00000367615.9	c.464_467delTTTT	p.Phe155CysfsTer25	frameshift_variant	Exon 4 of 8	1	NM_014625.4	ENSP00000356587.4
NPHS2	ENST00000367616.4	c.464_467delTTTT	p.Phe155CysfsTer29	frameshift_variant	Exon 4 of 7	1		ENSP00000356588.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424154 Hom.: 0 AF XY: 0.00000142 AC XY: 1 AN XY: 705956

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.20e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-179528880;