rs132630320
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_001399.5(EDA):c.1072C>G(p.Gln358Glu) variant causes a missense change involving the alteration of a 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 (no stars). Synonymous variant affecting the same amino acid position (i.e. Q358Q) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 21)
Consequence
EDA
NM_001399.5 missense
NM_001399.5 missense
Scores
8
4
3
Clinical Significance
Conservation
PhyloP100: 7.29
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 Likely_pathogenic. Variant got 7 ACMG points.
PM1
?
In a hotspot region, there are 6 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 2 benign, 3 uncertain in NM_001399.5
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.923
PP5
?
Variant X-70035505-C-G is Pathogenic according to our data. Variant chrX-70035505-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 11045.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDA | NM_001399.5 | c.1072C>G | p.Gln358Glu | missense_variant | 8/8 | ENST00000374552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.1072C>G | p.Gln358Glu | missense_variant | 8/8 | 1 | NM_001399.5 | P4 | |
EDA | ENST00000374553.6 | c.1066C>G | p.Gln356Glu | missense_variant | 8/8 | 1 | A1 | ||
EDA | ENST00000524573.5 | c.1057C>G | p.Gln353Glu | missense_variant | 8/8 | 1 | A1 | ||
EDA | ENST00000616899.1 | c.676C>G | p.Gln226Glu | missense_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 21
GnomAD3 genomes
?
Cov.:
21
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 21
GnomAD4 genome
?
Cov.:
21
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Tooth agenesis, selective, X-linked, 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 15, 2007 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
A;A;A
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;.;.
Sift4G
Benign
T;T;T;T
Polyphen
D;D;D;.
Vest4
MutPred
0.81
.;Loss of catalytic residue at Q358 (P = 0.0079);.;.;
MVP
MPC
1.8
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at