3-132690611-C-T

Position:

chr3-132690611-C-T

Variant summary

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

The NM_153240.5(NPHP3):c.2610G>A(p.Pro870Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0227 in 1,613,574 control chromosomes in the GnomAD database, including 835 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 268 hom., cov: 32)

Exomes 𝑓: 0.021 ( 567 hom. )

Consequence

NPHP3
NM_153240.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.21

Variant links:

Genes affected

NPHP3 (HGNC:7907): (nephrocystin 3) This gene encodes a protein containing a coiled-coil (CC) domain, a tubulin-tyrosine ligase (TTL) domain, and a tetratrico peptide repeat (TPR) domain. The encoded protein interacts with nephrocystin, it is required for normal ciliary development, and it functions in renal tubular development. Mutations in this gene are associated with nephronophthisis type 3, and also with renal-hepatic-pancreatic dysplasia, and Meckel syndrome type 7. Naturally occurring read-through transcripts exist between this gene and the downstream ACAD11 (acyl-CoA dehydrogenase family, member 11) gene. [provided by RefSeq, Feb 2011]

NPHP3 links:

NPHP3-ACAD11 (HGNC:48351): (NPHP3-ACAD11 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring NPHP3 (nephronophthisis 3, adolescent) and ACAD11 (acyl-CoA dehydrogenase family, member 11) genes on chromosome 3. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

NPHP3-ACAD11 links:

NPHP3 (HGNC:):

NPHP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 3-132690611-C-T is Benign according to our data. Variant chr3-132690611-C-T is described in ClinVar as [Benign]. Clinvar id is 96513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-132690611-C-T is described in Lovd as [Benign]. Variant chr3-132690611-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP3	NM_153240.5 linkuse as main transcript	c.2610G>A	p.Pro870Pro	synonymous_variant	19/27	ENST00000337331.10	NP_694972.3	Q7Z494-1
NPHP3-ACAD11	NR_037804.1 linkuse as main transcript	n.2616G>A		non_coding_transcript_exon_variant	18/45

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP3	ENST00000337331.10 linkuse as main transcript	c.2610G>A	p.Pro870Pro	synonymous_variant	19/27	1	NM_153240.5	ENSP00000338766.5		Q7Z494-1

Frequencies

GnomAD3 genomes

AF:

0.0427

AC:

6497

AN:

152018

Hom.:

268

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0203

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.0654

Gnomad SAS

AF:

0.0491

Gnomad FIN

AF:

0.00613

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0165

Gnomad OTH

AF:

0.0388

GnomAD3 exomes

AF:

0.0282

AC:

7092

AN:

251386

Hom.:

213

AF XY:

0.0279

AC XY:

3794

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.0119

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0669

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.00642

Gnomad NFE exome

AF:

0.0152

Gnomad OTH exome

AF:

0.0210

GnomAD4 exome

AF:

0.0206

AC:

30107

AN:

1461438

Hom.:

567

Cov.:

AF XY:

0.0211

AC XY:

15339

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0134

Gnomad4 ASJ exome

AF:

0.0209

Gnomad4 EAS exome

AF:

0.0454

Gnomad4 SAS exome

AF:

0.0464

Gnomad4 FIN exome

AF:

0.00670

Gnomad4 NFE exome

AF:

0.0158

Gnomad4 OTH exome

AF:

0.0268

GnomAD4 genome

AF:

0.0429

AC:

6520

AN:

152136

Hom.:

268

Cov.:

AF XY:

0.0413

AC XY:

3075

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.0202

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.0654

Gnomad4 SAS

AF:

0.0491

Gnomad4 FIN

AF:

0.00613

Gnomad4 NFE

AF:

0.0165

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0213

Hom.:

105

Bravo

AF:

0.0464

Asia WGS

AF:

0.0520

AC:

181

AN:

3478

EpiCase

AF:

0.0145

EpiControl

AF:

0.0171

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 15, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Oct 08, 2012	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Renal-hepatic-pancreatic dysplasia 1

Benign:1

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. -

NPHP3-related Meckel-like syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Nephronophthisis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Nephronophthisis 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.89

DANN

Benign

0.37

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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