NM_153240.5:c.3125+12dupT

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_153240.5(NPHP3):c.3125+12dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,613,178 control chromosomes in the GnomAD database, including 21,887 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2054 hom., cov: 30)

Exomes 𝑓: 0.14 ( 19833 hom. )

Consequence

NPHP3
NM_153240.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.44

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 3-132688637-T-TA is Benign according to our data. Variant chr3-132688637-T-TA is described in ClinVar as [Benign]. Clinvar id is 262702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPHP3	NM_153240.5 link	c.3125+12dupT		intron_variant	Intron 21 of 26	ENST00000337331.10	NP_694972.3	Q7Z494-1
NPHP3-ACAD11	NR_037804.1 link	n.3131+12dupT		intron_variant	Intron 20 of 44

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPHP3	ENST00000337331.10 link	c.3125+12_3125+13insT		intron_variant	Intron 21 of 26	1	NM_153240.5	ENSP00000338766.5		Q7Z494-1

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20987

AN:

152118

Hom.:

2063

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.0847

Gnomad EAS

AF:

0.582

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.170

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.134

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.161

AC:

39864

AN:

248228

Hom.:

5194

AF XY:

0.161

AC XY:

21635

AN XY:

134412

show subpopulations

Gnomad AFR exome

AF:

0.0894

Gnomad AMR exome

AF:

0.0761

Gnomad ASJ exome

AF:

0.0860

Gnomad EAS exome

AF:

0.586

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.144

AC:

210210

AN:

1460942

Hom.:

19833

Cov.:

AF XY:

0.145

AC XY:

105382

AN XY:

726812

show subpopulations

Gnomad4 AFR exome

AF:

0.0847

Gnomad4 AMR exome

AF:

0.0790

Gnomad4 ASJ exome

AF:

0.0863

Gnomad4 EAS exome

AF:

0.592

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.149

GnomAD4 genome

AF:

0.138

AC:

20975

AN:

152236

Hom.:

2054

Cov.:

AF XY:

0.143

AC XY:

10627

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0906

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.0847

Gnomad4 EAS

AF:

0.581

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.170

Gnomad4 NFE

AF:

0.134

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.125

Hom.:

241

Bravo

AF:

0.130

Asia WGS

AF:

0.317

AC:

1100

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Nephronophthisis

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Renal-hepatic-pancreatic dysplasia 1

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

May 24, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Meckel-Gruber syndrome

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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