rs1555725707
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000677123.1(PRKCSH):c.215dupA(p.Asn72LysfsTer12) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
PRKCSH
ENST00000677123.1 frameshift
ENST00000677123.1 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.58
Publications
1 publications found
Genes affected
PRKCSH (HGNC:9411): (PRKCSH beta subunit of glucosidase II) This gene encodes the beta-subunit of glucosidase II, an N-linked glycan-processing enzyme in the endoplasmic reticulum. The encoded protein is an acidic phosphoprotein known to be a substrate for protein kinase C. Mutations in this gene have been associated with the autosomal dominant polycystic liver disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
PRKCSH Gene-Disease associations (from GenCC):
- polycystic liver disease 1Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, Genomics England PanelApp
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-11437892-T-TA is Pathogenic according to our data. Variant chr19-11437892-T-TA is described in ClinVar as Pathogenic. ClinVar VariationId is 13243.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: ENST00000677123.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRKCSH | NM_001289104.2 | MANE Select | c.215dupA | p.Asn72LysfsTer12 | frameshift | Exon 4 of 18 | NP_001276033.1 | ||
| PRKCSH | NM_001289103.2 | c.215dupA | p.Asn72LysfsTer12 | frameshift | Exon 4 of 18 | NP_001276032.1 | |||
| PRKCSH | NM_001379608.1 | c.215dupA | p.Asn72LysfsTer12 | frameshift | Exon 4 of 18 | NP_001366537.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PRKCSH | ENST00000677123.1 | MANE Select | c.215dupA | p.Asn72LysfsTer12 | frameshift | Exon 4 of 18 | ENSP00000503163.1 | ||
| PRKCSH | ENST00000592741.5 | TSL:1 | c.215dupA | p.Asn72LysfsTer12 | frameshift | Exon 4 of 18 | ENSP00000466134.1 | ||
| PRKCSH | ENST00000589838.5 | TSL:1 | c.215dupA | p.Asn72LysfsTer12 | frameshift | Exon 3 of 17 | ENSP00000465461.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461858Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727228 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1461858
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
727228
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
1
AN:
53416
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111984
Other (OTH)
AF:
AC:
0
AN:
60392
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
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 as Germline
Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Polycystic liver disease 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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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