10-53827547-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001384140.1(PCDH15):c.4213C>G(p.Arg1405Gly) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001384140.1 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PCDH15 | NM_033056.4 | c.4213C>G | p.Arg1405Gly | missense_variant, splice_region_variant | Exon 32 of 33 | ENST00000320301.11 | NP_149045.3 | |
PCDH15 | NM_001384140.1 | c.4213C>G | p.Arg1405Gly | missense_variant, splice_region_variant | Exon 32 of 38 | ENST00000644397.2 | NP_001371069.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PCDH15 | ENST00000320301.11 | c.4213C>G | p.Arg1405Gly | missense_variant, splice_region_variant | Exon 32 of 33 | 1 | NM_033056.4 | ENSP00000322604.6 | ||
PCDH15 | ENST00000644397.2 | c.4213C>G | p.Arg1405Gly | missense_variant, splice_region_variant | Exon 32 of 38 | NM_001384140.1 | ENSP00000495195.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249056Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134822
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Arg1405Gly variant in PCDH15 has not been previously reported in individua ls with hearing loss or Usher syndrome, but has been identified in 1/17246 East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broa dinstitute.org/; dbSNP rs148046721). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic ro le. Computational prediction tools and conservation analyses suggest that this v ariant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Arg14 05Gly variant is uncertain. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at