rs143936796

Variant names:

• chr19-11436201-GTCC-G
• rs143936796
• NM_001289104.2:c.79+10_79+12delCCT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001289104.2(PRKCSH):​c.79+10_79+12delCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,583,422 control chromosomes in the GnomAD database, including 1,282 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (82 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1200 hom.)
• Consequence: PRKCSH NM_001289104.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.49
• 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 -16 ACMG points.

• BP6: Variant 19-11436201-GTCC-G is Benign according to our data. Variant chr19-11436201-GTCC-G is described in ClinVar as Benign. ClinVar VariationId is 94077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0298 (4443/149084) while in subpopulation NFE AF = 0.0379 (2576/67996). AF 95% confidence interval is 0.0367. There are 82 homozygotes in GnomAd4. There are 2360 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4443 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.79+10_79+12delCCT		intron	N/A	NP_001276033.1	K7ELL7
	PRKCSH	NM_001289103.2		c.79+10_79+12delCCT		intron	N/A	NP_001276032.1	K7ELL7
	PRKCSH	NM_001379608.1		c.79+10_79+12delCCT		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.79+10_79+12delCCT		intron	N/A	ENSP00000503163.1	K7ELL7
	PRKCSH	ENST00000592741.5	TSL:1	c.79+10_79+12delCCT		intron	N/A	ENSP00000466134.1	K7ELL7
	PRKCSH	ENST00000589838.5	TSL:1	c.79+10_79+12delCCT		intron	N/A	ENSP00000465461.1	P14314-1

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4441 AN: 148980 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.00707

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0319

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0179

GnomAD2 exomes AF: 0.0354 AC: 7147 AN: 201694 AF XY: 0.0342

Gnomad AFR exome AF: 0.00612

Gnomad AMR exome AF: 0.0588

Gnomad ASJ exome AF: 0.0115

Gnomad EAS exome AF: 0.0000678

Gnomad FIN exome AF: 0.0820

Gnomad NFE exome AF: 0.0374

Gnomad OTH exome AF: 0.0250

GnomAD4 exome AF: 0.0374 AC: 53590 AN: 1434338 Hom.: 1200 AF XY: 0.0361 AC XY: 25733 AN XY: 712028

African (AFR) AF: 0.00584 AC: 181 AN: 31016

American (AMR) AF: 0.0519 AC: 2072 AN: 39958

Ashkenazi Jewish (ASJ) AF: 0.0111 AC: 284 AN: 25632

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38078

South Asian (SAS) AF: 0.0162 AC: 1356 AN: 83816

European-Finnish (FIN) AF: 0.0774 AC: 3909 AN: 50516

Middle Eastern (MID) AF: 0.00540 AC: 31 AN: 5736

European-Non Finnish (NFE) AF: 0.0399 AC: 43858 AN: 1100192

Other (OTH) AF: 0.0320 AC: 1898 AN: 59394

GnomAD4 genome AF: 0.0298 AC: 4443 AN: 149084 Hom.: 82 Cov.: 32 AF XY: 0.0324 AC XY: 2360 AN XY: 72944

African (AFR) AF: 0.00705 AC: 272 AN: 38562

American (AMR) AF: 0.0319 AC: 484 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.0158 AC: 76 AN: 4822

European-Finnish (FIN) AF: 0.0884 AC: 937 AN: 10600

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0379 AC: 2576 AN: 67996

Other (OTH) AF: 0.0178 AC: 37 AN: 2084

Alfa AF: 0.0304 Hom.: 13

Bravo AF: 0.0256

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs143936796; hg19: chr19-11547022;