Variant 1-179575763-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014625.4(NPHS2):c.102A>G(p.Gly34Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.983 in 1,496,666 control chromosomes in the GnomAD database, including 723,969 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G34G?) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.95 ( 68595 hom., cov: 32)

Exomes 𝑓: 0.99 ( 655374 hom. )

Consequence

NPHS2
NM_014625.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.412

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 1-179575763-T-C is Benign according to our data. Variant chr1-179575763-T-C is described in ClinVar as [Benign]. Clinvar id is 260424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-179575763-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.412 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHS2	NM_014625.4 link	c.102A>G	p.Gly34Gly	synonymous_variant	1/8	ENST00000367615.9	NP_055440.1	Q9NP85-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHS2	ENST00000367615.9 link	c.102A>G	p.Gly34Gly	synonymous_variant	1/8	1	NM_014625.4	ENSP00000356587.4		Q9NP85-1
NPHS2	ENST00000367616.4 link	c.102A>G	p.Gly34Gly	synonymous_variant	1/7	1		ENSP00000356588.4		Q9NP85-2

Frequencies

GnomAD3 genomes

AF:

0.947

AC:

143975

AN:

151962

Hom.:

68551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.844

Gnomad AMI

AF:

0.962

Gnomad AMR

AF:

0.975

Gnomad ASJ

AF:

0.988

Gnomad EAS

AF:

0.978

Gnomad SAS

AF:

0.941

Gnomad FIN

AF:

0.994

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.993

Gnomad OTH

AF:

0.951

GnomAD3 exomes

AF:

0.977

AC:

96167

AN:

98386

Hom.:

47062

AF XY:

0.976

AC XY:

54163

AN XY:

55482

show subpopulations

Gnomad AFR exome

AF:

0.807

Gnomad AMR exome

AF:

0.986

Gnomad ASJ exome

AF:

0.989

Gnomad EAS exome

AF:

0.975

Gnomad SAS exome

AF:

0.945

Gnomad FIN exome

AF:

0.995

Gnomad NFE exome

AF:

0.993

Gnomad OTH exome

AF:

0.980

GnomAD4 exome

AF:

0.987

AC:

1327035

AN:

1344596

Hom.:

655374

Cov.:

AF XY:

0.986

AC XY:

654062

AN XY:

663274

show subpopulations

Gnomad4 AFR exome

AF:

0.838

Gnomad4 AMR exome

AF:

0.983

Gnomad4 ASJ exome

AF:

0.987

Gnomad4 EAS exome

AF:

0.977

Gnomad4 SAS exome

AF:

0.948

Gnomad4 FIN exome

AF:

0.995

Gnomad4 NFE exome

AF:

0.994

Gnomad4 OTH exome

AF:

0.977

GnomAD4 genome

AF:

0.947

AC:

144070

AN:

152070

Hom.:

68595

Cov.:

AF XY:

0.948

AC XY:

70438

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.844

Gnomad4 AMR

AF:

0.976

Gnomad4 ASJ

AF:

0.988

Gnomad4 EAS

AF:

0.978

Gnomad4 SAS

AF:

0.941

Gnomad4 FIN

AF:

0.994

Gnomad4 NFE

AF:

0.993

Gnomad4 OTH

AF:

0.951

Alfa

AF:

0.972

Hom.:

12293

Bravo

AF:

0.942

Asia WGS

AF:

0.942

AC:

3249

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 88. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Nephrotic syndrome, type 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Steroid-resistant nephrotic syndrome

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Nov 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.62

DANN

Benign

0.35

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over