rs35112233
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_003628.6(PKP4):c.66C>G(p.Ala22Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000684 in 1,461,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A22A) has been classified as Benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PKP4
NM_003628.6 synonymous
NM_003628.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.60
Publications
0 publications found
Genes affected
PKP4 (HGNC:9026): (plakophilin 4) Armadillo-like proteins are characterized by a series of armadillo repeats, first defined in the Drosophila 'armadillo' gene product, that are typically 42 to 45 amino acids in length. These proteins can be divided into subfamilies based on their number of repeats, their overall sequence similarity, and the dispersion of the repeats throughout their sequences. Members of the p120(ctn)/plakophilin subfamily of Armadillo-like proteins, including CTNND1, CTNND2, PKP1, PKP2, PKP4, and ARVCF. PKP4 may be a component of desmosomal plaque and other adhesion plaques and is thought to be involved in regulating junctional plaque organization and cadherin function. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 2-158533250-C-G is Benign according to our data. Variant chr2-158533250-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1754970.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003628.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PKP4 | MANE Select | c.66C>G | p.Ala22Ala | synonymous | Exon 2 of 22 | NP_003619.2 | Q99569-1 | ||
| PKP4 | c.66C>G | p.Ala22Ala | synonymous | Exon 2 of 22 | NP_001364147.1 | Q99569-1 | |||
| PKP4 | c.66C>G | p.Ala22Ala | synonymous | Exon 2 of 22 | NP_001291898.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PKP4 | TSL:1 MANE Select | c.66C>G | p.Ala22Ala | synonymous | Exon 2 of 22 | ENSP00000374409.3 | Q99569-1 | ||
| PKP4 | TSL:1 | c.66C>G | p.Ala22Ala | synonymous | Exon 2 of 21 | ENSP00000374407.3 | Q99569-2 | ||
| PKP4 | TSL:1 | n.66C>G | non_coding_transcript_exon | Exon 2 of 22 | ENSP00000396827.2 | E7EST6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727148 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461720
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
727148
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33478
American (AMR)
AF:
AC:
0
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39696
South Asian (SAS)
AF:
AC:
0
AN:
86240
European-Finnish (FIN)
AF:
AC:
0
AN:
53404
Middle Eastern (MID)
AF:
AC:
0
AN:
5738
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111938
Other (OTH)
AF:
AC:
0
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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