rs796052815
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PS1PM1PM2PP3_Strong
The NM_001184880.2(PCDH19):c.1335C>G(p.Asp445Glu) 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 Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin ClinVar.
Frequency
Consequence
NM_001184880.2 missense
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 |
---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.1335C>G | p.Asp445Glu | missense_variant | 1/6 | ENST00000373034.8 | |
PCDH19 | NM_001105243.2 | c.1335C>G | p.Asp445Glu | missense_variant | 1/5 | ||
PCDH19 | NM_020766.3 | c.1335C>G | p.Asp445Glu | missense_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.1335C>G | p.Asp445Glu | missense_variant | 1/6 | 1 | NM_001184880.2 | A1 | |
PCDH19 | ENST00000255531.8 | c.1335C>G | p.Asp445Glu | missense_variant | 1/5 | 1 | P5 | ||
PCDH19 | ENST00000420881.6 | c.1335C>G | p.Asp445Glu | missense_variant | 1/5 | 1 | A1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 29, 2016 | In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PCDH19-related disease. ClinVar contains an entry for this variant (Variation ID: 206331). This sequence change replaces aspartic acid with glutamic acid at codon 445 of the PCDH19 protein (p.Asp445Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at