Variant rs12631786 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153240.5(NPHP3):c.394-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 1,359,224 control chromosomes in the GnomAD database, including 26,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3561 hom., cov: 31)

Exomes 𝑓: 0.18 ( 23209 hom. )

Consequence

NPHP3
NM_153240.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0210

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 (HGNC:):

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-132719875-T-C is Benign according to our data. Variant chr3-132719875-T-C is described in ClinVar as [Benign]. Clinvar id is 262713.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 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.394-45A>G		intron_variant		ENST00000337331.10	NP_694972.3	Q7Z494-1
NPHP3-ACAD11	NR_037804.1 linkuse as main transcript	n.498-45A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPHP3	ENST00000337331.10 linkuse as main transcript	c.394-45A>G		intron_variant		1	NM_153240.5	ENSP00000338766.5		Q7Z494-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

30681

AN:

149458

Hom.:

3564

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.335

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.264

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.205

GnomAD3 exomes

AF:

0.227

AC:

41723

AN:

183714

Hom.:

5570

AF XY:

0.227

AC XY:

22606

AN XY:

99510

show subpopulations

Gnomad AFR exome

AF:

0.231

Gnomad AMR exome

AF:

0.177

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.568

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.178

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.182

AC:

220123

AN:

1209678

Hom.:

23209

Cov.:

AF XY:

0.185

AC XY:

111842

AN XY:

605490

show subpopulations

Gnomad4 AFR exome

AF:

0.213

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.215

Gnomad4 NFE exome

AF:

0.161

Gnomad4 OTH exome

AF:

0.202

GnomAD4 genome

AF:

0.205

AC:

30686

AN:

149546

Hom.:

3561

Cov.:

AF XY:

0.208

AC XY:

15200

AN XY:

72998

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.557

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.168

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.182

Hom.:

496

Bravo

AF:

0.203

Asia WGS

AF:

0.365

AC:

1258

AN:

3450

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.3

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