Genetic Variant PRKCSH:p.Glu320_Glu323del (chr19-11447525-AGAGGAGGAGGAG-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001289104.2(PRKCSH):c.957_968delGGAGGAGGAGGA(p.Glu320_Glu323del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,583,918 control chromosomes in the GnomAD database, including 1 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

PRKCSH
NM_001289104.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.27

Publications

11 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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001289104.2

BP6

Variant 19-11447525-AGAGGAGGAGGAG-A is Benign according to our data. Variant chr19-11447525-AGAGGAGGAGGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2051254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.000166 (238/1434292) while in subpopulation EAS AF = 0.00228 (89/39096). AF 95% confidence interval is 0.00189. There are 1 homozygotes in GnomAdExome4. There are 121 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCSH	NM_001289104.2 link	c.957_968delGGAGGAGGAGGA	p.Glu320_Glu323del	disruptive_inframe_deletion	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.957_968delGGAGGAGGAGGA	p.Glu320_Glu323del	disruptive_inframe_deletion	Exon 11 of 18		NM_001289104.2	ENSP00000503163.1		K7ELL7

Frequencies

GnomAD3 genomes

AF:

0.000114

AC:

AN:

149518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000741

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000163

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000166

AC:

238

AN:

1434292

Hom.:

AF XY:

0.000170

AC XY:

121

AN XY:

712772

show subpopulations

African (AFR)

AF:

0.0000912

AC:

AN:

32884

American (AMR)

AF:

0.0000952

AC:

AN:

42036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25668

East Asian (EAS)

AF:

0.00228

AC:

AN:

39096

South Asian (SAS)

AF:

0.000178

AC:

AN:

84050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51680

Middle Eastern (MID)

AF:

0.000902

AC:

AN:

5546

European-Non Finnish (NFE)

AF:

0.0000987

AC:

108

AN:

1093992

Other (OTH)

AF:

0.000236

AC:

AN:

59340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000114

AC:

AN:

149626

Hom.:

Cov.:

AF XY:

0.0000686

AC XY:

AN XY:

72902

show subpopulations

African (AFR)

AF:

0.0000739

AC:

AN:

40622

American (AMR)

AF:

0.0000663

AC:

AN:

15092

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.000396

AC:

AN:

5054

South Asian (SAS)

AF:

0.00

AC:

AN:

4678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000163

AC:

AN:

67348

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000108

Hom.:

370

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.3

Mutation Taster

=148/52

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAG

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