rs145708952

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHP3	NM_153240.5 link	c.3812+42C>T		intron_variant	Intron 26 of 26	ENST00000337331.10	NP_694972.3	Q7Z494-1
NPHP3-ACAD11	NR_037804.1 link	n.3818+42C>T		intron_variant	Intron 25 of 44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPHP3	ENST00000337331.10 link	c.3812+42C>T		intron_variant	Intron 26 of 26	1	NM_153240.5	ENSP00000338766.5		Q7Z494-1
NPHP3-ACAD11	ENST00000632629.1 link	c.458+42C>T		intron_variant	Intron 3 of 4	2		ENSP00000488520.1		A0A0J9YXS1

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

GnomAD2 exomes

AF:

0.00664

AC:

1659

AN:

249902

AF XY:

0.00691

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 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

African (AFR)

AF:

0.00147

AC:

AN:

23882

American (AMR)

AF:

0.00218

AC:

AN:

44012

Ashkenazi Jewish (ASJ)

AF:

0.000869

AC:

AN:

23004

East Asian (EAS)

AF:

0.0000538

AC:

AN:

37194

South Asian (SAS)

AF:

0.00800

AC:

608

AN:

75972

European-Finnish (FIN)

AF:

0.00492

AC:

262

AN:

53210

Middle Eastern (MID)

AF:

0.00185

AC:

AN:

4852

European-Non Finnish (NFE)

AF:

0.0103

AC:

6735

AN:

654470

Other (OTH)

AF:

0.00649

AC:

284

AN:

43778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

420

840

1259

1679

2099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00590

AC:

897

AN:

152134

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

446

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41526

American (AMR)

AF:

0.00432

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00850

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00748

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00941

AC:

640

AN:

67978

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

136

181

226

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.3

(source)

DANN

Benign

0.32

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over