Variant rs145708952 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153240.5(NPHP3):c.3812+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00804 in 1,112,508 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0059 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 49 hom. )

Consequence

NPHP3
NM_153240.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.157

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:):

NPHP3-ACAD11 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-132682661-G-A is Benign according to our data. Variant chr3-132682661-G-A is described in ClinVar as [Benign]. Clinvar id is 262711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0059 (897/152134) while in subpopulation NFE AF= 0.00941 (640/67978). AF 95% confidence interval is 0.00881. There are 2 homozygotes in gnomad4. There are 446 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHP3	NM_153240.5 linkuse as main transcript	c.3812+42C>T		intron_variant		ENST00000337331.10
NPHP3-ACAD11	NR_037804.1 linkuse as main transcript	n.3818+42C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPHP3	ENST00000337331.10 linkuse as main transcript	c.3812+42C>T		intron_variant		1	NM_153240.5	P1	Q7Z494-1

Frequencies

GnomAD3 genomes

AF:

0.00589

AC:

896

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00433

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.00748

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00941

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00664

AC:

1659

AN:

249902

Hom.:

AF XY:

0.00691

AC XY:

934

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00227

Gnomad ASJ exome

AF:

0.000896

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00726

Gnomad FIN exome

AF:

0.00551

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00345

GnomAD4 exome

AF:

0.00838

AC:

8051

AN:

960374

Hom.:

Cov.:

AF XY:

0.00837

AC XY:

4186

AN XY:

499872

show subpopulations

Gnomad4 AFR exome

AF:

0.00147

Gnomad4 AMR exome

AF:

0.00218

Gnomad4 ASJ exome

AF:

0.000869

Gnomad4 EAS exome

AF:

0.0000538

Gnomad4 SAS exome

AF:

0.00800

Gnomad4 FIN exome

AF:

0.00492

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00649

GnomAD4 genome

AF:

0.00590

AC:

897

AN:

152134

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00432

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00850

Gnomad4 FIN

AF:

0.00748

Gnomad4 NFE

AF:

0.00941

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00739

Hom.:

Bravo

AF:

0.00532

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

DANN

Benign

0.32

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