Genetic Variant PRKCSH:p.Glu321_Glu323del (chr19-11447525-AGAGGAGGAG-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001289104.2(PRKCSH):c.960_968delGGAGGAGGA(p.Glu321_Glu323del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000478 in 1,578,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

PRKCSH
NM_001289104.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.27

Publications

11 publications found

Variant links:

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 1
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, Genomics England PanelApp

PRKCSH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001289104.2

BP6

Variant 19-11447525-AGAGGAGGAG-A is Benign according to our data. Variant chr19-11447525-AGAGGAGGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 713728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000408 (61/149622) while in subpopulation SAS AF = 0.00214 (10/4678). AF 95% confidence interval is 0.00116. There are 0 homozygotes in GnomAd4. There are 35 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCSH	NM_001289104.2 link	c.960_968delGGAGGAGGA	p.Glu321_Glu323del	disruptive_inframe_deletion	Exon 11 of 18	ENST00000677123.1	NP_001276033.1	K7ELL7B4DJQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCSH	ENST00000677123.1 link	c.960_968delGGAGGAGGA	p.Glu321_Glu323del	disruptive_inframe_deletion	Exon 11 of 18		NM_001289104.2	ENSP00000503163.1		K7ELL7

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

149514

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000346

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00158

Gnomad SAS

AF:

0.00213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000386

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00117

AC:

205

AN:

175324

AF XY:

0.00127

show subpopulations

Gnomad AFR exome

AF:

0.000590

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.000913

Gnomad EAS exome

AF:

0.00256

Gnomad FIN exome

AF:

0.000315

Gnomad NFE exome

AF:

0.000940

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.000485

AC:

693

AN:

1428602

Hom.:

AF XY:

0.000497

AC XY:

353

AN XY:

709860

show subpopulations

African (AFR)

AF:

0.000335

AC:

AN:

32844

American (AMR)

AF:

0.000931

AC:

AN:

41912

Ashkenazi Jewish (ASJ)

AF:

0.000668

AC:

AN:

25456

East Asian (EAS)

AF:

0.00133

AC:

AN:

39094

South Asian (SAS)

AF:

0.00135

AC:

113

AN:

83886

European-Finnish (FIN)

AF:

0.0000969

AC:

AN:

51596

Middle Eastern (MID)

AF:

0.000543

AC:

AN:

5526

European-Non Finnish (NFE)

AF:

0.000381

AC:

415

AN:

1089212

Other (OTH)

AF:

0.000643

AC:

AN:

59076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000408

AC:

AN:

149622

Hom.:

Cov.:

AF XY:

0.000480

AC XY:

AN XY:

72898

show subpopulations

African (AFR)

AF:

0.000345

AC:

AN:

40622

American (AMR)

AF:

0.000199

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00158

AC:

AN:

5054

South Asian (SAS)

AF:

0.00214

AC:

AN:

4678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000386

AC:

AN:

67346

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00183

Hom.:

370

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PRKCSH: BS1, BS2 -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=196/4

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over