X-43963678-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000266.4(NDP):​c.-207-4826A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000272 in 110,430 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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 0.000027 (0 hom., 0 hem., cov: 22)
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000266.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDP	NM_000266.4	MANE Select	c.-207-4826A>T		intron	N/A	NP_000257.1
	NDP-AS1	NR_046631.1		n.576+2784T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDP	ENST00000642620.1	MANE Select	c.-207-4826A>T		intron	N/A	ENSP00000495972.1
	NDP	ENST00000647044.1		c.-208+2830A>T		intron	N/A	ENSP00000495811.1
	NDP-AS1	ENST00000435093.1	TSL:3	n.576+2784T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000272 AC: 3 AN: 110430 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000330

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: 0.0000379

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000272 AC: 3 AN: 110430 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32648

African (AFR) AF: 0.0000330 AC: 1 AN: 30279

American (AMR) AF: 0.00 AC: 0 AN: 10448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3472

South Asian (SAS) AF: 0.00 AC: 0 AN: 2628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5810

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 235

European-Non Finnish (NFE) AF: 0.0000379 AC: 2 AN: 52776

Other (OTH) AF: 0.00 AC: 0 AN: 1480

Alfa AF: 0.00 Hom.: 21040

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.39

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;