rs188406927

Variant names:

• chr19-11438134-T-C
• rs188406927
• NM_001289104.2:c.350+10T>C

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.350+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00725 in 1,613,816 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0074 (50 hom.)
• Consequence: PRKCSH NM_001289104.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.549
• 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=-0.59).
• BP6: Variant 19-11438134-T-C is Benign according to our data. Variant chr19-11438134-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258794.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 = 0.0054 (822/152216) while in subpopulation SAS AF = 0.0129 (62/4820). AF 95% confidence interval is 0.0103. There are 9 homozygotes in GnomAd4. There are 419 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 822 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.350+10T>C		intron	N/A	NP_001276033.1	K7ELL7
	PRKCSH	NM_001289103.2		c.350+10T>C		intron	N/A	NP_001276032.1	K7ELL7
	PRKCSH	NM_001379608.1		c.350+10T>C		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.350+10T>C		intron	N/A	ENSP00000503163.1	K7ELL7
	PRKCSH	ENST00000592741.5	TSL:1	c.350+10T>C		intron	N/A	ENSP00000466134.1	K7ELL7
	PRKCSH	ENST00000589838.5	TSL:1	c.350+10T>C		intron	N/A	ENSP00000465461.1	P14314-1

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 817 AN: 152098 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.00256

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.0129

Gnomad FIN AF: 0.00726

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00748

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00627 AC: 1573 AN: 250784 AF XY: 0.00695

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00805

Gnomad FIN exome AF: 0.00648

Gnomad NFE exome AF: 0.00710

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00745 AC: 10884 AN: 1461600 Hom.: 50 Cov.: 33 AF XY: 0.00768 AC XY: 5587 AN XY: 727054

African (AFR) AF: 0.00143 AC: 48 AN: 33464

American (AMR) AF: 0.00145 AC: 65 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00411 AC: 163 AN: 39692

South Asian (SAS) AF: 0.0129 AC: 1114 AN: 86208

European-Finnish (FIN) AF: 0.00534 AC: 285 AN: 53400

Middle Eastern (MID) AF: 0.00558 AC: 32 AN: 5738

European-Non Finnish (NFE) AF: 0.00792 AC: 8806 AN: 1111876

Other (OTH) AF: 0.00613 AC: 370 AN: 60384

GnomAD4 genome AF: 0.00540 AC: 822 AN: 152216 Hom.: 9 Cov.: 31 AF XY: 0.00563 AC XY: 419 AN XY: 74424

African (AFR) AF: 0.00101 AC: 42 AN: 41516

American (AMR) AF: 0.00255 AC: 39 AN: 15280

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

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

South Asian (SAS) AF: 0.0129 AC: 62 AN: 4820

European-Finnish (FIN) AF: 0.00726 AC: 77 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00748 AC: 509 AN: 68016

Other (OTH) AF: 0.00474 AC: 10 AN: 2110

Alfa AF: 0.00573 Hom.: 0

Bravo AF: 0.00479

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Polycystic liver disease 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism

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: rs188406927; hg19: chr19-11548955; COSMIC: COSV52953585; COSMIC: COSV52953585;