rs186375

Variant names:

• chr19-11447425-T-C
• rs186375
• NM_001289104.2:c.850-14T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-11447425-T-C
• chr19-11447425-T-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.850-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 1,613,382 control chromosomes in the GnomAD database, including 791,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (75015 hom., cov: 32)
  • Exomes 𝑓: 0.99 (716104 hom.)
• Consequence: PRKCSH NM_001289104.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.01
• Publications: 8 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=-0.92).
• BP6: Variant 19-11447425-T-C is Benign according to our data. Variant chr19-11447425-T-C is described in ClinVar as Benign. ClinVar VariationId is 94078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCSH	NM_001289104.2	MANE Select	c.850-14T>C		intron	N/A	NP_001276033.1	K7ELL7
	PRKCSH	NM_001289103.2		c.850-14T>C		intron	N/A	NP_001276032.1	K7ELL7
	PRKCSH	NM_001379608.1		c.850-14T>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.850-14T>C		intron	N/A	ENSP00000503163.1	K7ELL7
	PRKCSH	ENST00000592741.5	TSL:1	c.850-14T>C		intron	N/A	ENSP00000466134.1	K7ELL7
	PRKCSH	ENST00000589838.5	TSL:1	c.850-14T>C		intron	N/A	ENSP00000465461.1	P14314-1

Frequencies

GnomAD3 genomes AF: 0.993 AC: 151014 AN: 152134 Hom.: 74956 Cov.: 32

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.993

Gnomad FIN AF: 0.984

Gnomad MID AF: 1.00

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.994

GnomAD2 exomes AF: 0.992 AC: 246342 AN: 248298 AF XY: 0.992

Gnomad AFR exome AF: 0.999

Gnomad AMR exome AF: 0.997

Gnomad ASJ exome AF: 0.991

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.985

Gnomad NFE exome AF: 0.990

Gnomad OTH exome AF: 0.994

GnomAD4 exome AF: 0.990 AC: 1446577 AN: 1461130 Hom.: 716104 Cov.: 48 AF XY: 0.990 AC XY: 719644 AN XY: 726862

African (AFR) AF: 0.998 AC: 33421 AN: 33472

American (AMR) AF: 0.997 AC: 44573 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 25917 AN: 26124

East Asian (EAS) AF: 1.00 AC: 39696 AN: 39698

South Asian (SAS) AF: 0.993 AC: 85594 AN: 86216

European-Finnish (FIN) AF: 0.985 AC: 52297 AN: 53108

Middle Eastern (MID) AF: 0.998 AC: 5751 AN: 5762

European-Non Finnish (NFE) AF: 0.989 AC: 1099477 AN: 1111682

Other (OTH) AF: 0.992 AC: 59851 AN: 60364

GnomAD4 genome AF: 0.993 AC: 151132 AN: 152252 Hom.: 75015 Cov.: 32 AF XY: 0.992 AC XY: 73864 AN XY: 74424

African (AFR) AF: 0.998 AC: 41481 AN: 41564

American (AMR) AF: 0.997 AC: 15258 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3428 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5157 AN: 5158

South Asian (SAS) AF: 0.993 AC: 4789 AN: 4824

European-Finnish (FIN) AF: 0.984 AC: 10435 AN: 10608

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67283 AN: 68006

Other (OTH) AF: 0.994 AC: 2095 AN: 2108

Alfa AF: 0.991 Hom.: 13720

Bravo AF: 0.994

Asia WGS AF: 0.997 AC: 3465 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	not provided (3)
-	-	2	Polycystic liver disease 1 (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.28
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs186375; hg19: chr19-11558240;