19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAG

Variant names:

• chr19-11447525-AGAGGAG-A
• rs3217229
• NM_001289104.2:c.963_968delGGAGGA

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.963_968delGGAGGA​(p.Glu322_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 0.0868 in 1,471,316 control chromosomes in the GnomAD database, including 1,983 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (329 hom., cov: 0)
  • Exomes 𝑓: 0.089 (1654 hom.)
• Consequence: PRKCSH NM_001289104.2 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.27
• 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-AGAGGAG-A is Benign according to our data. Variant chr19-11447525-AGAGGAG-A is described in ClinVar as [Benign]. Clinvar id is 94080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCSH	NM_001289104.2	c.963_968delGGAGGA	p.Glu322_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.963_968delGGAGGA	p.Glu322_Glu323del	disruptive_inframe_deletion	Exon 11 of 18		NM_001289104.2	ENSP00000503163.1

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9579 AN: 149226 Hom.: 329 Cov.: 0

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.0337

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00573

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0923

GnomAD2 exomes AF: 0.0881 AC: 15453 AN: 175324 AF XY: 0.0906

Gnomad AFR exome AF: 0.0506

Gnomad AMR exome AF: 0.0787

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0140

Gnomad FIN exome AF: 0.0706

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0894 AC: 118178 AN: 1321984 Hom.: 1654 AF XY: 0.0888 AC XY: 58245 AN XY: 655686

African (AFR) AF: 0.0369 AC: 1052 AN: 28536

American (AMR) AF: 0.0727 AC: 2710 AN: 37294

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 2817 AN: 23508

East Asian (EAS) AF: 0.00534 AC: 195 AN: 36542

South Asian (SAS) AF: 0.0517 AC: 3935 AN: 76054

European-Finnish (FIN) AF: 0.0663 AC: 3004 AN: 45276

Middle Eastern (MID) AF: 0.104 AC: 535 AN: 5134

European-Non Finnish (NFE) AF: 0.0978 AC: 99309 AN: 1015876

Other (OTH) AF: 0.0859 AC: 4621 AN: 53764

GnomAD4 genome AF: 0.0642 AC: 9581 AN: 149332 Hom.: 329 Cov.: 0 AF XY: 0.0626 AC XY: 4554 AN XY: 72718

African (AFR) AF: 0.0290 AC: 1175 AN: 40572

American (AMR) AF: 0.0764 AC: 1150 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 359 AN: 3432

East Asian (EAS) AF: 0.00574 AC: 29 AN: 5052

South Asian (SAS) AF: 0.0349 AC: 163 AN: 4676

European-Finnish (FIN) AF: 0.0581 AC: 584 AN: 10056

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0874 AC: 5878 AN: 67256

Other (OTH) AF: 0.0918 AC: 188 AN: 2048

Alfa AF: 0.0873 Hom.: 370

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jun 01, 2015

Eurofins Ntd Llc (ga)

Significance: 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		=195/5	polymorphism (auto)

Splicing

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: COSV52950186; COSMIC: COSV52950186;