Variant rs398124547 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_153240.5(NPHP3):c.3126-4del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000734 in 1,216,238 control chromosomes in the GnomAD database, including 2 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 2 hom. )

Consequence

NPHP3
NM_153240.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.265

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 -16 ACMG points.

BP6

Variant 3-132687229-TA-T is Benign according to our data. Variant chr3-132687229-TA-T is described in ClinVar as [Benign]. Clinvar id is 96515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-132687229-TA-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00066 (100/151480) while in subpopulation AMR AF= 0.00558 (85/15226). AF 95% confidence interval is 0.00463. There are 0 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPHP3	NM_153240.5 linkuse as main transcript	c.3126-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000337331.10	NP_694972.3
NPHP3-ACAD11	NR_037804.1 linkuse as main transcript	n.3132-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP3	ENST00000337331.10 linkuse as main transcript	c.3126-4del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_153240.5	ENSP00000338766	P1	Q7Z494-1

Frequencies

GnomAD3 genomes

AF:

0.000661

AC:

100

AN:

151366

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00559

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.00198

AC:

434

AN:

219134

Hom.:

AF XY:

0.00144

AC XY:

172

AN XY:

119050

show subpopulations

Gnomad AFR exome

AF:

0.000410

Gnomad AMR exome

AF:

0.0132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000256

Gnomad FIN exome

AF:

0.000241

Gnomad NFE exome

AF:

0.000131

Gnomad OTH exome

AF:

0.000741

GnomAD4 exome

AF:

0.000745

AC:

793

AN:

1064758

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

336

AN XY:

545916

show subpopulations

Gnomad4 AFR exome

AF:

0.000427

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0000430

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.000156

Gnomad4 FIN exome

AF:

0.000190

Gnomad4 NFE exome

AF:

0.000317

Gnomad4 OTH exome

AF:

0.000747

GnomAD4 genome

AF:

0.000660

AC:

100

AN:

151480

Hom.:

Cov.:

AF XY:

0.000770

AC XY:

AN XY:

74024

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00558

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.000869

Hom.:

Bravo

AF:

0.00144

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 22, 2015

- -

Nephronophthisis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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