rs11557488

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001289104.2(PRKCSH):c.871G>A(p.Ala291Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,538 control chromosomes in the GnomAD database, including 34,463 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2480 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31983 hom. )

Consequence

PRKCSH
NM_001289104.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.75

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:

PRKCSH (HGNC:):

PRKCSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055055916).

BP6

Variant 19-11447460-G-A is Benign according to our data. Variant chr19-11447460-G-A is described in ClinVar as [Benign]. Clinvar id is 94079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCSH	NM_001289104.2 linkuse as main transcript	c.871G>A	p.Ala291Thr	missense_variant	11/18	ENST00000677123.1	NP_001276033.1	K7ELL7B4DJQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCSH	ENST00000677123.1 linkuse as main transcript	c.871G>A	p.Ala291Thr	missense_variant	11/18		NM_001289104.2	ENSP00000503163.1		K7ELL7

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23662

AN:

152062

Hom.:

2482

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.333

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0802

Gnomad EAS

AF:

0.0235

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.291

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.169

AC:

42149

AN:

249196

Hom.:

4419

AF XY:

0.171

AC XY:

23047

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.0466

Gnomad AMR exome

AF:

0.124

Gnomad ASJ exome

AF:

0.0916

Gnomad EAS exome

AF:

0.0273

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.201

AC:

294348

AN:

1461358

Hom.:

31983

Cov.:

AF XY:

0.199

AC XY:

144691

AN XY:

726962

show subpopulations

Gnomad4 AFR exome

AF:

0.0427

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.0896

Gnomad4 EAS exome

AF:

0.0226

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.288

Gnomad4 NFE exome

AF:

0.223

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.155

AC:

23655

AN:

152180

Hom.:

2480

Cov.:

AF XY:

0.157

AC XY:

11669

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.0802

Gnomad4 EAS

AF:

0.0236

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.291

Gnomad4 NFE

AF:

0.221

Gnomad4 OTH

AF:

0.140

Alfa

AF:

0.188

Hom.:

4601

Bravo

AF:

0.140

TwinsUK

AF:

0.228

AC:

846

ALSPAC

AF:

0.221

AC:

851

ESP6500AA

AF:

0.0592

AC:

261

ESP6500EA

AF:

0.216

AC:

1855

ExAC

AF:

0.172

AC:

20847

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.198

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:2

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

Polycystic liver disease 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

.;T;.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.69

.;T;T;T

MetaRNN

Benign

0.0055

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;M;M

PrimateAI

Benign

0.28

Sift4G

Benign

0.49

T;T;T;T

Polyphen

0.0030

.;.;.;B

Vest4

0.092

ClinPred

0.0047

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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