rs188406927

chr19-11438134-T-C

Variant summary

Our verdict is Benign. Variant got -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:4
• Conservation: PhyloP100: 0.549

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 -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 [Likely_benign]. Clinvar id 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 817 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2	c.350+10T>C		intron_variant		ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1	c.350+10T>C		intron_variant			NM_001289104.2	A2

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

GnomAD3 exomes AF: 0.00627 AC: 1573 AN: 250784 Hom.: 6 AF XY: 0.00695 AC XY: 942 AN XY: 135572

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 SAS exome AF: 0.0121

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

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00411

Gnomad4 SAS exome AF: 0.0129

Gnomad4 FIN exome AF: 0.00534

Gnomad4 NFE exome AF: 0.00792

Gnomad4 OTH exome AF: 0.00613

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

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00791

Gnomad4 SAS AF: 0.0129

Gnomad4 FIN AF: 0.00726

Gnomad4 NFE AF: 0.00748

Gnomad4 OTH AF: 0.00474

Alfa AF: 0.00573 Hom.: 0

Bravo AF: 0.00479

Asia WGS AF: 0.0110 AC: 38 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 16, 2024	- -

not specified Benign:1

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

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	13
Dann	Benign	0.83

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