rs778782448
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001184880.2(PCDH19):c.3412C>T(p.Pro1138Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,209,129 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001184880.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDH19 | NM_001184880.2 | c.3412C>T | p.Pro1138Ser | missense_variant | Exon 6 of 6 | ENST00000373034.8 | NP_001171809.1 | |
PCDH19 | NM_001105243.2 | c.3271C>T | p.Pro1091Ser | missense_variant | Exon 5 of 5 | NP_001098713.1 | ||
PCDH19 | NM_020766.3 | c.3268C>T | p.Pro1090Ser | missense_variant | Exon 5 of 5 | NP_065817.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH19 | ENST00000373034.8 | c.3412C>T | p.Pro1138Ser | missense_variant | Exon 6 of 6 | 1 | NM_001184880.2 | ENSP00000362125.4 | ||
PCDH19 | ENST00000255531.8 | c.3271C>T | p.Pro1091Ser | missense_variant | Exon 5 of 5 | 1 | ENSP00000255531.7 | |||
PCDH19 | ENST00000420881.6 | c.3268C>T | p.Pro1090Ser | missense_variant | Exon 5 of 5 | 1 | ENSP00000400327.2 | |||
PCDH19 | ENST00000464981.1 | n.-12C>T | upstream_gene_variant | 3 | ENSP00000479805.1 |
Frequencies
GnomAD3 genomes AF: 0.0000179 AC: 2AN: 111788Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33970
GnomAD3 exomes AF: 0.000143 AC: 26AN: 181603Hom.: 0 AF XY: 0.000118 AC XY: 8AN XY: 67533
GnomAD4 exome AF: 0.0000237 AC: 26AN: 1097341Hom.: 0 Cov.: 30 AF XY: 0.0000221 AC XY: 8AN XY: 362715
GnomAD4 genome AF: 0.0000179 AC: 2AN: 111788Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33970
ClinVar
Submissions by phenotype
not specified Benign:1
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Inborn genetic diseases Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
PCDH19-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Developmental and epileptic encephalopathy, 9 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at