rs1079292

Variant names:

• chr1-179575763-T-A
• rs1079292
• NM_014625.4:c.102A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-179575763-T-A
• chr1-179575763-T-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014625.4(NPHS2):​c.102A>T​(p.Gly34Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. G34G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NPHS2 NM_014625.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 18 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: Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, G2P
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHS2	NM_014625.4	MANE Select	c.102A>T	p.Gly34Gly	synonymous	Exon 1 of 8	NP_055440.1
	NPHS2	NM_001297575.2		c.102A>T	p.Gly34Gly	synonymous	Exon 1 of 7	NP_001284504.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPHS2	ENST00000367615.9	TSL:1 MANE Select	c.102A>T	p.Gly34Gly	synonymous	Exon 1 of 8	ENSP00000356587.4
	NPHS2	ENST00000367616.4	TSL:1	c.102A>T	p.Gly34Gly	synonymous	Exon 1 of 7	ENSP00000356588.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1344748 Hom.: 0 Cov.: 63 AF XY: 0.00 AC XY: 0 AN XY: 663376

African (AFR) AF: 0.00 AC: 0 AN: 27516

American (AMR) AF: 0.00 AC: 0 AN: 28344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23100

East Asian (EAS) AF: 0.00 AC: 0 AN: 32302

South Asian (SAS) AF: 0.00 AC: 0 AN: 73390

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38124

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5002

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061260

Other (OTH) AF: 0.00 AC: 0 AN: 55710

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.36
DANN	Benign	0.49
PhyloP100		-0.41
PromoterAI		-0.093	Neutral
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: rs1079292; hg19: chr1-179544898;