X-43956960-T-C

Variant names:

• chrX-43956960-T-C
• rs766117
• NM_000266.4:c.174+1512A>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.174+1512A>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 0.55 (12291 hom., 17526 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: NDP NM_000266.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• 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=-0.94).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDP	NM_000266.4	MANE Select	c.174+1512A>G		intron	N/A	NP_000257.1	Q00604
	NDP-AS1	NR_046631.1		n.466+2412T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NDP	ENST00000642620.1	MANE Select	c.174+1512A>G		intron	N/A	ENSP00000495972.1	Q00604
	NDP	ENST00000647044.1		c.174+1512A>G		intron	N/A	ENSP00000495811.1	Q00604
	NDP	ENST00000868527.1		c.174+1512A>G		intron	N/A	ENSP00000538586.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 60723 AN: 110621 Hom.: 12289 Cov.: 23

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.555

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: 0.549 AC: 60757 AN: 110673 Hom.: 12291 Cov.: 23 AF XY: 0.532 AC XY: 17526 AN XY: 32919

African (AFR) AF: 0.647 AC: 19709 AN: 30451

American (AMR) AF: 0.518 AC: 5408 AN: 10439

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1348 AN: 2637

East Asian (EAS) AF: 0.424 AC: 1488 AN: 3508

South Asian (SAS) AF: 0.435 AC: 1141 AN: 2621

European-Finnish (FIN) AF: 0.439 AC: 2576 AN: 5862

Middle Eastern (MID) AF: 0.590 AC: 125 AN: 212

European-Non Finnish (NFE) AF: 0.528 AC: 27844 AN: 52762

Other (OTH) AF: 0.556 AC: 838 AN: 1507

Alfa AF: 0.536 Hom.: 68531

Bravo AF: 0.561

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.72
DANN	Benign	0.33
PhyloP100		-0.55
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs766117;

hg19: chrX-43816206;