19-11436201-GTCC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001289104.2(PRKCSH):c.79+10_79+12del variant causes a splice donor region, 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 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.49

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4441 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2	c.79+10_79+12del		splice_donor_region_variant, intron_variant		ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1	c.79+10_79+12del		splice_donor_region_variant, intron_variant			NM_001289104.2	A2

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

GnomAD3 exomes AF: 0.0354 AC: 7147 AN: 201694 Hom.: 189 AF XY: 0.0342 AC XY: 3738 AN XY: 109450

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 SAS exome AF: 0.0153

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

Gnomad4 AFR exome AF: 0.00584

Gnomad4 AMR exome AF: 0.0519

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.0000263

Gnomad4 SAS exome AF: 0.0162

Gnomad4 FIN exome AF: 0.0774

Gnomad4 NFE exome AF: 0.0399

Gnomad4 OTH exome AF: 0.0320

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

Gnomad4 AFR AF: 0.00705

Gnomad4 AMR AF: 0.0319

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0158

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.0379

Gnomad4 OTH AF: 0.0178

Alfa AF: 0.0304 Hom.: 13

Bravo AF: 0.0256

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 10, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Polycystic liver disease 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs143936796; hg19: chr19-11547022;