Variant 19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAGGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

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 (★★).

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

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.52

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
PRKCSH	NM_001289104.2 link	c.966_968delGGA	p.Glu323del	disruptive_inframe_deletion	11/18	ENST00000677123.1	NP_001276033.1	K7ELL7B4DJQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCSH	ENST00000677123.1 link	c.966_968delGGA	p.Glu323del	disruptive_inframe_deletion	11/18		NM_001289104.2	ENSP00000503163.1		K7ELL7

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

57320

AN:

149204

Hom.:

11063

Cov.:

show subpopulations

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

show subpopulations

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

show subpopulations

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.:

AF XY:

0.385

AC XY:

28018

AN XY:

72742

show subpopulations

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

LINK: link

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

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 29, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over