1-201293981-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001005337.3(PKP1):c.242G>A(p.Gly81Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,613,724 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G81R) has been classified as Likely benign.
Frequency
Consequence
NM_001005337.3 missense
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 |
---|---|---|---|---|---|---|---|---|
PKP1 | NM_001005337.3 | c.242G>A | p.Gly81Glu | missense_variant | Exon 2 of 14 | ENST00000367324.8 | NP_001005337.1 | |
PKP1 | NM_000299.4 | c.242G>A | p.Gly81Glu | missense_variant | Exon 2 of 15 | NP_000290.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PKP1 | ENST00000367324.8 | c.242G>A | p.Gly81Glu | missense_variant | Exon 2 of 14 | 1 | NM_001005337.3 | ENSP00000356293.4 | ||
PKP1 | ENST00000263946.7 | c.242G>A | p.Gly81Glu | missense_variant | Exon 2 of 15 | 5 | ENSP00000263946.3 | |||
PKP1 | ENST00000352845.3 | c.242G>A | p.Gly81Glu | missense_variant | Exon 2 of 14 | 5 | ENSP00000295597.3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250996Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135666
GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461624Hom.: 0 Cov.: 30 AF XY: 0.0000481 AC XY: 35AN XY: 727092
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152100Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74302
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 20, 2024 | The c.242G>A (p.G81E) alteration is located in exon 2 (coding exon 2) of the PKP1 gene. This alteration results from a G to A substitution at nucleotide position 242, causing the glycine (G) at amino acid position 81 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The PKP1 p.G81E variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs769244881) and in control databases in 13 of 282392 chromosomes at a frequency of 0.00004604 (Genome Aggregation Database March 6, 2019, v2.1.1). The p.G81 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at