5-140801845-T-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_018906.3(PCDHA3):c.648T>A(p.Asp216Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_018906.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDHA3 | NM_018906.3 | c.648T>A | p.Asp216Glu | missense_variant | Exon 1 of 4 | ENST00000522353.3 | NP_061729.1 | |
PCDHA1 | NM_018900.4 | c.2394+13161T>A | intron_variant | Intron 1 of 3 | ENST00000504120.4 | NP_061723.1 | ||
PCDHA2 | NM_018905.3 | c.2388+4493T>A | intron_variant | Intron 1 of 3 | ENST00000526136.2 | NP_061728.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDHA3 | ENST00000522353.3 | c.648T>A | p.Asp216Glu | missense_variant | Exon 1 of 4 | 1 | NM_018906.3 | ENSP00000429808.2 | ||
PCDHA1 | ENST00000504120.4 | c.2394+13161T>A | intron_variant | Intron 1 of 3 | 1 | NM_018900.4 | ENSP00000420840.3 | |||
PCDHA2 | ENST00000526136.2 | c.2388+4493T>A | intron_variant | Intron 1 of 3 | 1 | NM_018905.3 | ENSP00000431748.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152168Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251364Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135888
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461778Hom.: 0 Cov.: 89 AF XY: 0.00000413 AC XY: 3AN XY: 727186
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.648T>A (p.D216E) alteration is located in exon 1 (coding exon 1) of the PCDHA3 gene. This alteration results from a T to A substitution at nucleotide position 648, causing the aspartic acid (D) at amino acid position 216 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at