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
NM_000266.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.64
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]
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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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NDP | ENST00000642620.1 | c.334_349dupGGGGGCATGCGACTCA | p.Thr117ArgfsTer37 | frameshift_variant | Exon 3 of 3 | NM_000266.4 | ENSP00000495972.1 | |||
NDP | ENST00000647044.1 | c.334_349dupGGGGGCATGCGACTCA | p.Thr117ArgfsTer37 | frameshift_variant | Exon 4 of 4 | ENSP00000495811.1 | ||||
NDP-AS1 | ENST00000435093.1 | n.125_140dupTCGCATGCCCCCTGAG | non_coding_transcript_exon_variant | Exon 1 of 5 | 3 | |||||
NDP | ENST00000470584.1 | n.378_393dupGGGGGCATGCGACTCA | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 23
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:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.