chrX-43949823-A-T
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_000266.4(NDP):c.378T>A(p.Cys126*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
NDP
NM_000266.4 stop_gained
NM_000266.4 stop_gained
Scores
2
2
1
Clinical Significance
Conservation
PhyloP100: 5.35
Publications
1 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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 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 5 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant X-43949823-A-T is Pathogenic according to our data. Variant chrX-43949823-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 3249907.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.378T>A | p.Cys126* | stop_gained | Exon 3 of 3 | NM_000266.4 | ENSP00000495972.1 | |||
| NDP | ENST00000647044.1 | c.378T>A | p.Cys126* | stop_gained | Exon 4 of 4 | ENSP00000495811.1 | ||||
| NDP-AS1 | ENST00000435093.1 | n.92A>T | non_coding_transcript_exon_variant | Exon 1 of 5 | 3 | |||||
| NDP | ENST00000470584.1 | n.422T>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1067314Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 347654
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1067314
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
347654
African (AFR)
AF:
AC:
0
AN:
25641
American (AMR)
AF:
AC:
0
AN:
30070
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
18782
East Asian (EAS)
AF:
AC:
0
AN:
28383
South Asian (SAS)
AF:
AC:
0
AN:
50580
European-Finnish (FIN)
AF:
AC:
0
AN:
38586
Middle Eastern (MID)
AF:
AC:
0
AN:
4102
European-Non Finnish (NFE)
AF:
AC:
0
AN:
826166
Other (OTH)
AF:
AC:
0
AN:
45004
GnomAD4 genome
GnomAD4 genome
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinal dystrophy Pathogenic:1
Jan 01, 2007
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Significance:Pathogenic
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
FATHMM_MKL
Uncertain
D
PhyloP100
Vest4
0.89
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.