Genetic Variant PRKCSH:p.Pro20Pro (chr19-11436177-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001289104.2(PRKCSH):c.60C>T(p.Pro20Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,592,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

PRKCSH
NM_001289104.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0690

Publications

0 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: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

PRKCSH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 19-11436177-C-T is Benign according to our data. Variant chr19-11436177-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 754953.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.069 with no splicing effect.

BS2

High AC in GnomAd4 at 15 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001289104.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKCSH	NM_001289104.2	MANE Select	c.60C>T	p.Pro20Pro	synonymous	Exon 2 of 18	NP_001276033.1	K7ELL7
PRKCSH	NM_001289103.2		c.60C>T	p.Pro20Pro	synonymous	Exon 2 of 18	NP_001276032.1	K7ELL7
PRKCSH	NM_001379608.1		c.60C>T	p.Pro20Pro	synonymous	Exon 2 of 18	NP_001366537.1	P14314-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRKCSH	ENST00000677123.1	MANE Select	c.60C>T	p.Pro20Pro	synonymous	Exon 2 of 18	ENSP00000503163.1	K7ELL7
PRKCSH	ENST00000592741.5	TSL:1	c.60C>T	p.Pro20Pro	synonymous	Exon 2 of 18	ENSP00000466134.1	K7ELL7
PRKCSH	ENST00000589838.5	TSL:1	c.60C>T	p.Pro20Pro	synonymous	Exon 1 of 17	ENSP00000465461.1	P14314-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000242

AC:

AN:

206602

AF XY:

0.00000891

show subpopulations

Gnomad AFR exome

AF:

0.000320

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000833

AC:

AN:

1439910

Hom.:

Cov.:

AF XY:

0.00000979

AC XY:

AN XY:

715128

show subpopulations

African (AFR)

AF:

0.000335

AC:

AN:

32798

American (AMR)

AF:

0.00

AC:

AN:

41060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25730

East Asian (EAS)

AF:

0.00

AC:

AN:

38074

South Asian (SAS)

AF:

0.00

AC:

AN:

84004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102480

Other (OTH)

AF:

0.00

AC:

AN:

59650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000986

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41548

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68000

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000992

Hom.:

Bravo

AF:

0.0000680

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Polycystic liver disease 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.069

PromoterAI

0.075

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over