Variant X-43949796-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000266.4(NDP):c.*3C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000737 in 1,166,550 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 22 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000077 ( 0 hom. 21 hem. )

Consequence

NDP
NM_000266.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

NDP (HGNC:7678): (norrin cystine knot growth factor NDP) This gene encodes a secreted protein with a cystein-knot motif that activates the Wnt/beta-catenin pathway. The protein forms disulfide-linked oligomers in the extracellular matrix. Mutations in this gene result in Norrie disease and X-linked exudative vitreoretinopathy. [provided by RefSeq, Feb 2009]

NDP links:

NDP-AS1 (HGNC:40395): (NDP antisense RNA 1)

NDP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS2

High Hemizygotes in GnomAdExome4 at 21 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDP	NM_000266.4 link	c.*3C>A		3_prime_UTR_variant	3/3	ENST00000642620.1	NP_000257.1	Q00604
NDP-AS1	NR_046631.1 link	n.65G>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDP	ENST00000642620 link	c.*3C>A	3_prime_UTR_variant	3/3		NM_000266.4	ENSP00000495972.1	Q00604
NDP	ENST00000647044 link	c.*3C>A	3_prime_UTR_variant	4/4			ENSP00000495811.1	Q00604
NDP-AS1	ENST00000435093.1 link	n.65G>T	non_coding_transcript_exon_variant	1/5	3
NDP	ENST00000470584.1 link	n.449C>A	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000446

AC:

AN:

112169

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34329

show subpopulations

Gnomad AFR

AF:

0.0000649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000830

AC:

AN:

120499

Hom.:

AF XY:

0.0000731

AC XY:

AN XY:

41047

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000768

AC:

AN:

1054381

Hom.:

Cov.:

AF XY:

0.0000614

AC XY:

AN XY:

342281

show subpopulations

Gnomad4 AFR exome

AF:

0.0000398

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000790

Gnomad4 NFE exome

AF:

0.0000880

Gnomad4 OTH exome

AF:

0.000112

GnomAD4 genome

AF:

0.0000446

AC:

AN:

112169

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

34329

show subpopulations

Gnomad4 AFR

AF:

0.0000649

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Athena Diagnostics

Mar 05, 2019

- -

NDP-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 07, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.3

DANN

Benign

0.79

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