rs397516661
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001399.5(EDA):c.347T>A(p.Leu116Ter) variant causes a stop gained 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 (★). Synonymous variant affecting the same amino acid position (i.e. L116L) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001399.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EDA | NM_001399.5 | c.347T>A | p.Leu116Ter | stop_gained | 1/8 | ENST00000374552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.347T>A | p.Leu116Ter | stop_gained | 1/8 | 1 | NM_001399.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Hypohidrotic X-linked ectodermal dysplasia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 04, 2011 | The Leu116X variant has not been reported in the literature nor previously ident ified by our laboratory. The variant leads to a premature stop codon at positio n 116, which is predicted to lead to a truncated or absent protein. Therefore, t his variant meets our criteria to be classified as pathogenic. The presence of a hemizygous pathogenic variant in EDA is consistent with a diagnosis of X-linked hypohidrotic ectodermal dysplasia, but this information should be reconciled wi th the complete clinical history of this individual. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at