19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAGGAG

Variant names:

• chr19-11447525-AGAG-A
• rs3217229
• NM_001289104.2:c.966_968delGGA

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_001289104.2(PRKCSH):​c.966_968delGGA​(p.Glu323del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E322E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.38 (11077 hom., cov: 0)
  • Exomes 𝑓: 0.34 (21790 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKCSH NM_001289104.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.52
• Publications: 11 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 1

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

ACMG classification

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

• BP3: Nonframeshift variant in repetitive region in NM_001289104.2
• BP6: Variant 19-11447525-AGAG-A is Benign according to our data. Variant chr19-11447525-AGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 94081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCSH	NM_001289104.2	c.966_968delGGA	p.Glu323del	disruptive_inframe_deletion	Exon 11 of 18	ENST00000677123.1	NP_001276033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCSH	ENST00000677123.1	c.966_968delGGA	p.Glu323del	disruptive_inframe_deletion	Exon 11 of 18		NM_001289104.2	ENSP00000503163.1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 57320 AN: 149204 Hom.: 11063 Cov.: 0

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.358 AC: 62705 AN: 175324 AF XY: 0.356

Gnomad AFR exome AF: 0.408

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.313

Gnomad EAS exome AF: 0.357

Gnomad FIN exome AF: 0.398

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.343

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.337 AC: 444031 AN: 1318978 Hom.: 21790 AF XY: 0.338 AC XY: 220162 AN XY: 650656

African (AFR) AF: 0.397 AC: 12116 AN: 30530

American (AMR) AF: 0.365 AC: 13674 AN: 37504

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 7439 AN: 22712

East Asian (EAS) AF: 0.378 AC: 10130 AN: 26832

South Asian (SAS) AF: 0.361 AC: 24947 AN: 69024

European-Finnish (FIN) AF: 0.402 AC: 18417 AN: 45818

Middle Eastern (MID) AF: 0.343 AC: 1753 AN: 5118

European-Non Finnish (NFE) AF: 0.328 AC: 336738 AN: 1028028

Other (OTH) AF: 0.352 AC: 18817 AN: 53412

GnomAD4 genome AF: 0.384 AC: 57362 AN: 149312 Hom.: 11077 Cov.: 0 AF XY: 0.385 AC XY: 28018 AN XY: 72742

African (AFR) AF: 0.441 AC: 17882 AN: 40554

American (AMR) AF: 0.380 AC: 5721 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1096 AN: 3434

East Asian (EAS) AF: 0.298 AC: 1504 AN: 5048

South Asian (SAS) AF: 0.333 AC: 1556 AN: 4674

European-Finnish (FIN) AF: 0.412 AC: 4156 AN: 10080

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.357 AC: 23988 AN: 67234

Other (OTH) AF: 0.390 AC: 800 AN: 2050

Alfa AF: 0.265 Hom.: 370

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 20, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic liver disease 1 Benign:2

Oct 25, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 29, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5
Mutation Taster		=55/45	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3217229; hg19: chr19-11558340; COSMIC: COSV52950109; COSMIC: COSV52950109;