chrX-69616309-A-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_001399.5(EDA):c.1A>G(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. 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: 24)
Consequence
EDA
NM_001399.5 start_lost
NM_001399.5 start_lost
Scores
8
3
2
Clinical Significance
Conservation
PhyloP100: 2.45
Genes affected
EDA (HGNC:3157): (ectodysplasin A) The protein encoded by this gene is a type II membrane protein that can be cleaved by furin to produce a secreted form. The encoded protein, which belongs to the tumor necrosis factor family, acts as a homotrimer and may be involved in cell-cell signaling during the development of ectodermal organs. Defects in this gene are a cause of ectodermal dysplasia, anhidrotic, which is also known as X-linked hypohidrotic ectodermal dysplasia. Several transcript variants encoding many different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_001399.5 (EDA) was described as [Pathogenic] in ClinVar as 44190
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-69616309-A-G is Pathogenic according to our data. Variant chrX-69616309-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 1070893.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDA | NM_001399.5 | c.1A>G | p.Met1? | start_lost | 1/8 | ENST00000374552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.1A>G | p.Met1? | start_lost | 1/8 | 1 | NM_001399.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hypohidrotic X-linked ectodermal dysplasia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2020 | For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individual(s) with ectodermal dysplasia (PMID: 24330993, 18076698, 20979233, 11378824). This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the EDA mRNA. The next in-frame methionine is located at codon 133. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D;D
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;.;.
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
P;P;P;B;B;B
Vest4
MutPred
Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);Loss of solvent accessibility (P = 0.3103);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.