rs145708952

chr3-132682661-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157

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-ACAD11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPHP3	NM_153240.5	c.3812+42C>T		intron_variant		ENST00000337331.10
NPHP3-ACAD11	NR_037804.1	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	c.3812+42C>T		intron_variant		1	NM_153240.5	P1

Frequencies

GnomAD3 genomes AF: 0.00589 AC: 896 AN: 152018 Hom.: 2 Cov.: 33

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.: 14 AF XY: 0.00691 AC XY: 934 AN XY: 135152

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.: 49 Cov.: 13 AF XY: 0.00837 AC XY: 4186 AN XY: 499872

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.: 2 Cov.: 33 AF XY: 0.00599 AC XY: 446 AN XY: 74396

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.: 1

Bravo AF: 0.00532

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.90
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

Other links and lift over

dbSNP: rs145708952; hg19: chr3-132401505;