X-69616270-GGCTCCCGGGCCTCAAGAGAGTGGGTGTCTCCGGAGGCCATGGGCTACCCGGAGGTGGAGCGCAGGGAACTCCTGCCTGCAGCA-G
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001399.5(EDA):c.-36_47delTCCCGGGCCTCAAGAGAGTGGGTGTCTCCGGAGGCCATGGGCTACCCGGAGGTGGAGCGCAGGGAACTCCTGCCTGCAGCAGC(p.Met1fs) variant causes a frameshift, start lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_001399.5 frameshift, start_lost
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
EDA | NM_001399.5 | c.-36_47delTCCCGGGCCTCAAGAGAGTGGGTGTCTCCGGAGGCCATGGGCTACCCGGAGGTGGAGCGCAGGGAACTCCTGCCTGCAGCAGC | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 8 | ENST00000374552.9 | NP_001390.1 | |
EDA | NM_001399.5 | c.-36_47delTCCCGGGCCTCAAGAGAGTGGGTGTCTCCGGAGGCCATGGGCTACCCGGAGGTGGAGCGCAGGGAACTCCTGCCTGCAGCAGC | 5_prime_UTR_variant | Exon 1 of 8 | ENST00000374552.9 | NP_001390.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.-36_47delTCCCGGGCCTCAAGAGAGTGGGTGTCTCCGGAGGCCATGGGCTACCCGGAGGTGGAGCGCAGGGAACTCCTGCCTGCAGCAGC | p.Met1fs | frameshift_variant, start_lost | Exon 1 of 8 | 1 | NM_001399.5 | ENSP00000363680.4 | ||
EDA | ENST00000374552 | c.-36_47delTCCCGGGCCTCAAGAGAGTGGGTGTCTCCGGAGGCCATGGGCTACCCGGAGGTGGAGCGCAGGGAACTCCTGCCTGCAGCAGC | 5_prime_UTR_variant | Exon 1 of 8 | 1 | NM_001399.5 | ENSP00000363680.4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Hypohidrotic X-linked ectodermal dysplasia Pathogenic:1
This variant is a gross deletion of the genomic region encompassing part of exon 1 (c.-36_47del) of the EDA gene, which includes the initiator codon. This is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with EDA-related conditions. Loss-of-function variants in EDA are known to be pathogenic (PMID: 9683615). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at