rs11557488

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 12/19 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

Publications

25 publications found

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 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

PRKCSH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PRKCSH	NM_001289104.2 link	c.871G>A	p.Ala291Thr	missense_variant	Exon 11 of 18	ENST00000677123.1	NP_001276033.1	K7ELL7B4DJQ5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCSH	ENST00000677123.1 link	c.871G>A	p.Ala291Thr	missense_variant	Exon 11 of 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

GnomAD2 exomes

AF:

0.169

AC:

42149

AN:

249196

AF XY:

0.171

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 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

African (AFR)

AF:

0.0427

AC:

1430

AN:

33478

American (AMR)

AF:

0.122

AC:

5437

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0896

AC:

2335

AN:

26064

East Asian (EAS)

AF:

0.0226

AC:

898

AN:

39700

South Asian (SAS)

AF:

0.112

AC:

9686

AN:

86234

European-Finnish (FIN)

AF:

0.288

AC:

15331

AN:

53234

Middle Eastern (MID)

AF:

0.103

AC:

593

AN:

5758

European-Non Finnish (NFE)

AF:

0.223

AC:

247910

AN:

1111802

Other (OTH)

AF:

0.178

AC:

10728

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

15251

30502

45752

61003

76254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8272

16544

24816

33088

41360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.155

AC:

23655

AN:

152180

Hom.:

2480

Cov.:

AF XY:

0.157

AC XY:

11669

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0505

AC:

2099

AN:

41554

American (AMR)

AF:

0.125

AC:

1908

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0802

AC:

278

AN:

3466

East Asian (EAS)

AF:

0.0236

AC:

122

AN:

5178

South Asian (SAS)

AF:

0.108

AC:

523

AN:

4828

European-Finnish (FIN)

AF:

0.291

AC:

3079

AN:

10574

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15003

AN:

67970

Other (OTH)

AF:

0.140

AC:

295

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

967

1934

2900

3867

4834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.193

Hom.:

10243

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

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 20, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic liver disease 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

(source)

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

PhyloP100

1.8

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over