19-11448343-A-G

Variant names:

• chr19-11448343-A-G
• rs160841
• NM_001289104.2:c.1196+52A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001289104.2(PRKCSH):​c.1196+52A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,546,554 control chromosomes in the GnomAD database, including 9,045 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2743 hom., cov: 32)
  • Exomes 𝑓: 0.083 (6302 hom.)
• Consequence: PRKCSH NM_001289104.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0780
• Publications: 7 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-11448343-A-G is Benign according to our data. Variant chr19-11448343-A-G is described in ClinVar as Benign. ClinVar VariationId is 1181148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCSH	NM_001289104.2	MANE Select	c.1196+52A>G		intron	N/A	NP_001276033.1
	PRKCSH	NM_001289103.2		c.1196+52A>G		intron	N/A	NP_001276032.1
	PRKCSH	NM_001379608.1		c.1175+52A>G		intron	N/A	NP_001366537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCSH	ENST00000677123.1	MANE Select	c.1196+52A>G		intron	N/A	ENSP00000503163.1
	PRKCSH	ENST00000592741.5	TSL:1	c.1196+52A>G		intron	N/A	ENSP00000466134.1
	PRKCSH	ENST00000589838.5	TSL:1	c.1175+52A>G		intron	N/A	ENSP00000465461.1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23766 AN: 151930 Hom.: 2729 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.0869

Gnomad FIN AF: 0.0806

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.116 AC: 19178 AN: 165672 AF XY: 0.110

Gnomad AFR exome AF: 0.321

Gnomad AMR exome AF: 0.169

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.0857

Gnomad NFE exome AF: 0.0725

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.0829 AC: 115536 AN: 1394504 Hom.: 6302 Cov.: 29 AF XY: 0.0826 AC XY: 56910 AN XY: 688996

African (AFR) AF: 0.323 AC: 10321 AN: 31952

American (AMR) AF: 0.165 AC: 5959 AN: 36040

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2562 AN: 25116

East Asian (EAS) AF: 0.131 AC: 4811 AN: 36654

South Asian (SAS) AF: 0.0959 AC: 7642 AN: 79682

European-Finnish (FIN) AF: 0.0824 AC: 4086 AN: 49570

Middle Eastern (MID) AF: 0.105 AC: 479 AN: 4582

European-Non Finnish (NFE) AF: 0.0686 AC: 73590 AN: 1073052

Other (OTH) AF: 0.105 AC: 6086 AN: 57856

GnomAD4 genome AF: 0.157 AC: 23839 AN: 152050 Hom.: 2743 Cov.: 32 AF XY: 0.156 AC XY: 11564 AN XY: 74324

African (AFR) AF: 0.316 AC: 13122 AN: 41482

American (AMR) AF: 0.167 AC: 2559 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0971 AC: 337 AN: 3470

East Asian (EAS) AF: 0.160 AC: 825 AN: 5164

South Asian (SAS) AF: 0.0866 AC: 417 AN: 4818

European-Finnish (FIN) AF: 0.0806 AC: 852 AN: 10576

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0751 AC: 5102 AN: 67950

Other (OTH) AF: 0.151 AC: 318 AN: 2108

Alfa AF: 0.102 Hom.: 323

Bravo AF: 0.172

Asia WGS AF: 0.158 AC: 547 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-0.078
Mutation Taster		=100/0	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: rs160841; hg19: chr19-11559158; COSMIC: COSV52951665; COSMIC: COSV52951665;