X-43963678-T-C

Position:

• chrX-43963678-T-C

Variant summary

Our verdict is Likely benign. Variant got -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

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

Verdict is Likely_benign. Variant got -4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NDP	NM_000266.4	c.-207-4826A>G		intron_variant		ENST00000642620.1	NP_000257.1
NDP-AS1	NR_046631.1	n.576+2784T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NDP	ENST00000642620.1	c.-207-4826A>G		intron_variant			NM_000266.4	ENSP00000495972	P1
NDP-AS1	ENST00000435093.1	n.576+2784T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.647 AC: 71413 AN: 110385 Hom.: 16601 Cov.: 22 AF XY: 0.642 AC XY: 20948 AN XY: 32629

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

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.687

Gnomad4 NFE AF: 0.671

Gnomad4 OTH AF: 0.674

Alfa AF: 0.631 Hom.: 18957

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

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: rs209766; hg19: chrX-43822924;