rs150798392

Variant names:

• chr19-11448643-A-G
• rs150798392
• NM_001289104.2:c.1286+14A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001289104.2(PRKCSH):​c.1286+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 1,612,458 control chromosomes in the GnomAD database, including 60 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: 32)
  • Exomes 𝑓: 0.0076 (51 hom.)
• Consequence: PRKCSH NM_001289104.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.07
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-11448643-A-G is Benign according to our data. Variant chr19-11448643-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00556 (847/152342) while in subpopulation SAS AF = 0.0131 (63/4826). AF 95% confidence interval is 0.0105. There are 9 homozygotes in GnomAd4. There are 428 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 847 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCSH	NM_001289104.2	MANE Select	c.1286+14A>G		intron	N/A	NP_001276033.1	K7ELL7
	PRKCSH	NM_001289103.2		c.1286+14A>G		intron	N/A	NP_001276032.1	K7ELL7
	PRKCSH	NM_001379608.1		c.1265+14A>G		intron	N/A	NP_001366537.1	P14314-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCSH	ENST00000677123.1	MANE Select	c.1286+14A>G		intron	N/A	ENSP00000503163.1	K7ELL7
	PRKCSH	ENST00000592741.5	TSL:1	c.1286+14A>G		intron	N/A	ENSP00000466134.1	K7ELL7
	PRKCSH	ENST00000589838.5	TSL:1	c.1265+14A>G		intron	N/A	ENSP00000465461.1	P14314-1

Frequencies

GnomAD3 genomes AF: 0.00553 AC: 842 AN: 152224 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00636 AC: 1597 AN: 250976 AF XY: 0.00704

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00816

Gnomad FIN exome AF: 0.00649

Gnomad NFE exome AF: 0.00727

Gnomad OTH exome AF: 0.00622

GnomAD4 exome AF: 0.00757 AC: 11047 AN: 1460116 Hom.: 51 Cov.: 31 AF XY: 0.00779 AC XY: 5659 AN XY: 726526

African (AFR) AF: 0.00150 AC: 50 AN: 33440

American (AMR) AF: 0.00148 AC: 66 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00421 AC: 167 AN: 39688

South Asian (SAS) AF: 0.0130 AC: 1117 AN: 86222

European-Finnish (FIN) AF: 0.00532 AC: 284 AN: 53338

Middle Eastern (MID) AF: 0.00538 AC: 31 AN: 5764

European-Non Finnish (NFE) AF: 0.00807 AC: 8961 AN: 1110496

Other (OTH) AF: 0.00615 AC: 371 AN: 60330

GnomAD4 genome AF: 0.00556 AC: 847 AN: 152342 Hom.: 9 Cov.: 32 AF XY: 0.00575 AC XY: 428 AN XY: 74490

African (AFR) AF: 0.00111 AC: 46 AN: 41586

American (AMR) AF: 0.00255 AC: 39 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00791 AC: 41 AN: 5186

South Asian (SAS) AF: 0.0131 AC: 63 AN: 4826

European-Finnish (FIN) AF: 0.00753 AC: 80 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00773 AC: 526 AN: 68028

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00667 Hom.: 0

Bravo AF: 0.00493

Asia WGS AF: 0.0100 AC: 35 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Polycystic liver disease 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.53
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs150798392; hg19: chr19-11559458; COSMIC: COSV52953620; COSMIC: COSV52953620;