chrX-70035503-G-C
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PS1_ModeratePM1PM2PM5PP3_Moderate
The NM_001399.5(EDA):c.1070G>C(p.Arg357Pro) variant causes a missense change. 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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R357W) 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.1070G>C | p.Arg357Pro | missense_variant | 8/8 | ENST00000374552.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EDA | ENST00000374552.9 | c.1070G>C | p.Arg357Pro | missense_variant | 8/8 | 1 | NM_001399.5 | P4 | |
EDA | ENST00000374553.6 | c.1064G>C | p.Arg355Pro | missense_variant | 8/8 | 1 | A1 | ||
EDA | ENST00000524573.5 | c.1055G>C | p.Arg352Pro | missense_variant | 8/8 | 1 | A1 | ||
EDA | ENST00000616899.1 | c.674G>C | p.Arg225Pro | missense_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes Cov.: 21
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 21
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 26, 2011 | Variant classified as Uncertain Significance - Favor Pathogenic. The Arg357Pro v ariant in EDA has been identified in one individual with X-linked hypohidrotic e ctodermal dysplasia and was absent from 60 control chromosomes (Monreal 1998). I n addition, modeling of the structure of the EDA protein shows that this variant clusters on the surface of the protein with several other variants and could af fect binding sites or folding of the protein (Hymowitz, 2003). This variant was identified in one control individual as reported in dbSNP (rs61747506); however, the case was a female so she could represent an unaffected carrier state. In su mmary, the clinical significance cannot be determined with certainty at this tim e; however, we would lean towards a more likely pathogenic effect. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at