rs132630308
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_ModeratePP5_Moderate
The NM_001399.5(EDA):c.181T>A(p.Tyr61Asn) variant causes a missense 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 Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y61H) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001399.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDA | NM_001399.5 | c.181T>A | p.Tyr61Asn | missense_variant | 1/8 | ENST00000374552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.181T>A | p.Tyr61Asn | missense_variant | 1/8 | 1 | NM_001399.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
Hypohidrotic X-linked ectodermal dysplasia Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 03, 2020 | Variants that disrupt the p.Tyr61 amino acid residue in EDA have been observed in affected individuals (PMID: 8696334). This suggests that it is a clinically significant residue, and that other variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This sequence change replaces tyrosine with asparagine at codon 61 of the EDA protein (p.Tyr61Asn). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and asparagine. This variant has been observed in an individual affected with ectodermal dysplasia (Invitae). This variant is not present in population databases (ExAC no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at