Variant chrX-43949785-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000266.4(NDP):c.*14G>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 0.00263 in 1,162,669 control chromosomes in the GnomAD database, including 48 homozygotes. There are 853 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.014 ( 25 hom., 442 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 23 hom. 411 hem. )

Consequence

NDP
NM_000266.4 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.899

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant X-43949785-C-T is Benign according to our data. Variant chrX-43949785-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 588627.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (1546/112221) while in subpopulation AFR AF= 0.0481 (1483/30857). AF 95% confidence interval is 0.046. There are 25 homozygotes in gnomad4. There are 442 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDP	NM_000266.4 link	c.*14G>A		3_prime_UTR_variant	3/3	ENST00000642620.1	NP_000257.1	Q00604
NDP-AS1	NR_046631.1 link	n.54C>T		non_coding_transcript_exon_variant	1/6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NDP	ENST00000642620 link	c.*14G>A	3_prime_UTR_variant	3/3		NM_000266.4	ENSP00000495972.1	Q00604
NDP	ENST00000647044 link	c.*14G>A	3_prime_UTR_variant	4/4			ENSP00000495811.1	Q00604
NDP-AS1	ENST00000435093.1 link	n.54C>T	non_coding_transcript_exon_variant	1/5	3
NDP	ENST00000470584.1 link	n.460G>A	non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0137

AC:

1533

AN:

112167

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

429

AN XY:

34313

show subpopulations

Gnomad AFR

AF:

0.0477

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00423

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:

0.0000751

Gnomad OTH

AF:

0.00993

GnomAD3 exomes

AF:

0.00365

AC:

431

AN:

118142

Hom.:

AF XY:

0.00252

AC XY:

103

AN XY:

40926

show subpopulations

Gnomad AFR exome

AF:

0.0497

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000698

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000861

Gnomad OTH exome

AF:

0.00238

GnomAD4 exome

AF:

0.00144

AC:

1517

AN:

1050448

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

411

AN XY:

339968

show subpopulations

Gnomad4 AFR exome

AF:

0.0499

Gnomad4 AMR exome

AF:

0.00252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000147

Gnomad4 OTH exome

AF:

0.00399

GnomAD4 genome

AF:

0.0138

AC:

1546

AN:

112221

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

442

AN XY:

34377

show subpopulations

Gnomad4 AFR

AF:

0.0481

Gnomad4 AMR

AF:

0.00413

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000751

Gnomad4 OTH

AF:

0.00981

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.0161

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

History of neurodevelopmental disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2013

There is insufficient or conflicting evidence for classification of this alteration. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.0

DANN

Benign

0.88

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