chr19-11436184-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001289104.2(PRKCSH):c.67G>C(p.Val23Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
PRKCSH
NM_001289104.2 missense
NM_001289104.2 missense
Scores
2
10
2
Clinical Significance
Conservation
PhyloP100: 8.36
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKCSH | NM_001289104.2 | c.67G>C | p.Val23Leu | missense_variant | 2/18 | ENST00000677123.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKCSH | ENST00000677123.1 | c.67G>C | p.Val23Leu | missense_variant | 2/18 | NM_001289104.2 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2022 | The c.67G>C (p.V23L) alteration is located in exon 2 (coding exon 1) of the PRKCSH gene. This alteration results from a G to C substitution at nucleotide position 67, causing the valine (V) at amino acid position 23 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.;.;.;.;.;M;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;.;.;.;.;.;.;.;D
Vest4
MutPred
Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);Loss of methylation at K18 (P = 0.0839);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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