rs62638749

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001289104.2(PRKCSH):c.549T>C(p.Ala183Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00736 in 1,612,054 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0056 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0075 ( 52 hom. )

Consequence

PRKCSH
NM_001289104.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -5.61

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-11442466-T-C is Benign according to our data. Variant chr19-11442466-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11442466-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-5.61 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00559 (850/152002) while in subpopulation SAS AF= 0.0133 (64/4808). AF 95% confidence interval is 0.0107. There are 9 homozygotes in gnomad4. There are 431 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 850 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCSH	NM_001289104.2 link	c.549T>C	p.Ala183Ala	synonymous_variant	Exon 7 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.549T>C	p.Ala183Ala	synonymous_variant	Exon 7 of 18		NM_001289104.2	ENSP00000503163.1		K7ELL7

Frequencies

GnomAD3 genomes

AF:

0.00557

AC:

846

AN:

151884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.00263

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00791

Gnomad SAS

AF:

0.0135

Gnomad FIN

AF:

0.00757

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00769

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00639

AC:

1597

AN:

249802

Hom.:

AF XY:

0.00706

AC XY:

953

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.00156

Gnomad AMR exome

AF:

0.00151

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00806

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.00646

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00754

AC:

11011

AN:

1460052

Hom.:

Cov.:

AF XY:

0.00776

AC XY:

5638

AN XY:

726202

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00411

Gnomad4 SAS exome

AF:

0.0131

Gnomad4 FIN exome

AF:

0.00536

Gnomad4 NFE exome

AF:

0.00801

Gnomad4 OTH exome

AF:

0.00619

GnomAD4 genome

AF:

0.00559

AC:

850

AN:

152002

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

431

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00121

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00792

Gnomad4 SAS

AF:

0.0133

Gnomad4 FIN

AF:

0.00757

Gnomad4 NFE

AF:

0.00769

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00601

Hom.:

Bravo

AF:

0.00496

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00567

EpiControl

AF:

0.00744

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 11, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PRKCSH: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic liver disease 1

Benign:1

Jan 13, 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

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.0070

DANN

Benign

0.66

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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