X-43963678-T-C

Variant names:

• chrX-43963678-T-C
• rs209766
• NM_000266.4:c.-207-4826A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000266.4(NDP):​c.-207-4826A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (16609 hom., 20996 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: NDP NM_000266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.393
• Publications: 3 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NDP	NM_000266.4	c.-207-4826A>G		intron_variant	Intron 1 of 2	ENST00000642620.1	NP_000257.1
NDP-AS1	NR_046631.1	n.576+2784T>C		intron_variant	Intron 4 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NDP	ENST00000642620.1	c.-207-4826A>G		intron_variant	Intron 1 of 2		NM_000266.4	ENSP00000495972.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 71413 AN: 110385 Hom.: 16601 Cov.: 22

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.687

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.679

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.647 AC: 71468 AN: 110439 Hom.: 16609 Cov.: 22 AF XY: 0.642 AC XY: 20996 AN XY: 32693

African (AFR) AF: 0.601 AC: 18219 AN: 30330

American (AMR) AF: 0.714 AC: 7462 AN: 10455

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 1736 AN: 2628

East Asian (EAS) AF: 0.549 AC: 1896 AN: 3453

South Asian (SAS) AF: 0.412 AC: 1079 AN: 2621

European-Finnish (FIN) AF: 0.687 AC: 3993 AN: 5809

Middle Eastern (MID) AF: 0.645 AC: 138 AN: 214

European-Non Finnish (NFE) AF: 0.671 AC: 35399 AN: 52757

Other (OTH) AF: 0.674 AC: 1009 AN: 1498

Alfa AF: 0.634 Hom.: 21040

Bravo AF: 0.656

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.63
PhyloP100		0.39
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs209766; hg19: chrX-43822924;