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

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001289104.2(PRKCSH):c.966_968dup(p.Glu324dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T312T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.042 ( 141 hom., cov: 0)

Exomes 𝑓: 0.037 ( 135 hom. )

Consequence

PRKCSH
NM_001289104.2 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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:

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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-A-AGAG is Benign according to our data. Variant chr19-11447525-A-AGAG is described in ClinVar as [Benign]. Clinvar id is 1260325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0419 (6261/149576) while in subpopulation AFR AF= 0.051 (2069/40602). AF 95% confidence interval is 0.0491. There are 141 homozygotes in gnomad4. There are 3010 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAd4 at 6261 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2 linkuse as main transcript	c.966_968dup	p.Glu324dup	inframe_insertion	11/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1 linkuse as main transcript	c.966_968dup	p.Glu324dup	inframe_insertion	11/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes

AF:

0.0419

AC:

6257

AN:

149468

Hom.:

141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0510

Gnomad AMI

AF:

0.0112

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0416

Gnomad EAS

AF:

0.00395

Gnomad SAS

AF:

0.00619

Gnomad FIN

AF:

0.0548

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0414

Gnomad OTH

AF:

0.0483

GnomAD3 exomes

AF:

0.0337

AC:

5909

AN:

175324

Hom.:

AF XY:

0.0324

AC XY:

3093

AN XY:

95328

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.0369

Gnomad ASJ exome

AF:

0.0398

Gnomad EAS exome

AF:

0.00611

Gnomad SAS exome

AF:

0.00977

Gnomad FIN exome

AF:

0.0519

Gnomad NFE exome

AF:

0.0363

Gnomad OTH exome

AF:

0.0434

GnomAD4 exome

AF:

0.0367

AC:

52682

AN:

1433844

Hom.:

135

Cov.:

AF XY:

0.0358

AC XY:

25478

AN XY:

712564

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.0302

Gnomad4 ASJ exome

AF:

0.0355

Gnomad4 EAS exome

AF:

0.00263

Gnomad4 SAS exome

AF:

0.00884

Gnomad4 FIN exome

AF:

0.0494

Gnomad4 NFE exome

AF:

0.0395

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0419

AC:

6261

AN:

149576

Hom.:

141

Cov.:

AF XY:

0.0413

AC XY:

3010

AN XY:

72882

show subpopulations

Gnomad4 AFR

AF:

0.0510

Gnomad4 AMR

AF:

0.0355

Gnomad4 ASJ

AF:

0.0416

Gnomad4 EAS

AF:

0.00376

Gnomad4 SAS

AF:

0.00620

Gnomad4 FIN

AF:

0.0548

Gnomad4 NFE

AF:

0.0414

Gnomad4 OTH

AF:

0.0478

Bravo

AF:

0.0420

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2020	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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