19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAGGAG

Position:

• chr19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAGGAG

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_001289104.2(PRKCSH):​c.966_968del​(p.Glu325del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar 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 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.52

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]

ACMG classification

Verdict is Benign. Variant got -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. Variant chr19-11447525-AGAG-A is described in Lovd as [Likely_benign]. Variant chr19-11447525-AGAG-A is described in Lovd as [Benign]. Variant chr19-11447525-AGAG-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
PRKCSH	NM_001289104.2	c.966_968del	p.Glu325del	inframe_deletion	11/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1	c.966_968del	p.Glu325del	inframe_deletion	11/18		NM_001289104.2	A2

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

GnomAD3 exomes AF: 0.358 AC: 62705 AN: 175324 Hom.: 3732 AF XY: 0.356 AC XY: 33954 AN XY: 95328

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 SAS exome AF: 0.348

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

Gnomad4 AFR exome AF: 0.397

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.378

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.402

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.352

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

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.380

Gnomad4 ASJ AF: 0.319

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.390

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 20, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Polycystic liver disease 1 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3217229; hg19: chr19-11558340;