chrX-43949851-G-GTGAGTCGCATGCCCCC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_000266.4(NDP):​c.334_349dupGGGGGCATGCGACTCA​(p.Thr117ArgfsTer37) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 23)

Consequence

NDP
NM_000266.4 frameshift

Scores

Not classified

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.64
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-AS1 (HGNC:40395): (NDP antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 20 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-43949851-G-GTGAGTCGCATGCCCCC is Pathogenic according to our data. Variant chrX-43949851-G-GTGAGTCGCATGCCCCC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3382646.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NDPNM_000266.4 linkc.334_349dupGGGGGCATGCGACTCA p.Thr117ArgfsTer37 frameshift_variant Exon 3 of 3 ENST00000642620.1 NP_000257.1 Q00604
NDP-AS1NR_046631.1 linkn.125_140dupTCGCATGCCCCCTGAG non_coding_transcript_exon_variant Exon 1 of 6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NDPENST00000642620.1 linkc.334_349dupGGGGGCATGCGACTCA p.Thr117ArgfsTer37 frameshift_variant Exon 3 of 3 NM_000266.4 ENSP00000495972.1 Q00604
NDPENST00000647044.1 linkc.334_349dupGGGGGCATGCGACTCA p.Thr117ArgfsTer37 frameshift_variant Exon 4 of 4 ENSP00000495811.1 Q00604
NDP-AS1ENST00000435093.1 linkn.125_140dupTCGCATGCCCCCTGAG non_coding_transcript_exon_variant Exon 1 of 5 3
NDPENST00000470584.1 linkn.378_393dupGGGGGCATGCGACTCA non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Atrophia bulborum hereditaria;C1844579:Exudative vitreoretinopathy 2, X-linked Pathogenic:1
-
Juno Genomics, Hangzhou Juno Genomics, Inc
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing

PVS1_Strong+PM2_Supporting+PP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-43809097; API