19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAG

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BS1 BS2

The NM_001289104.2(PRKCSH):c.960_968del(p.Glu323_Glu325del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000478 in 1,578,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00049 (0 hom.)
• Consequence: PRKCSH NM_001289104.2 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.27

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 -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001289104.2
• BP6: Variant 19-11447525-AGAGGAGGAG-A is Benign according to our data. Variant chr19-11447525-AGAGGAGGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 713728.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 = 0.000408 (61/149622) while in subpopulation SAS AF= 0.00214 (10/4678). AF 95% confidence interval is 0.00116. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 61 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2	c.960_968del	p.Glu323_Glu325del	inframe_deletion	11/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1	c.960_968del	p.Glu323_Glu325del	inframe_deletion	11/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes AF: 0.000408 AC: 61 AN: 149514 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000199

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.00213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000386

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00117 AC: 205 AN: 175324 Hom.: 1 AF XY: 0.00127 AC XY: 121 AN XY: 95328

Gnomad AFR exome AF: 0.000590

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.000913

Gnomad EAS exome AF: 0.00256

Gnomad SAS exome AF: 0.00181

Gnomad FIN exome AF: 0.000315

Gnomad NFE exome AF: 0.000940

Gnomad OTH exome AF: 0.00161

GnomAD4 exome AF: 0.000485 AC: 693 AN: 1428602 Hom.: 0 AF XY: 0.000497 AC XY: 353 AN XY: 709860

Gnomad4 AFR exome AF: 0.000335

Gnomad4 AMR exome AF: 0.000931

Gnomad4 ASJ exome AF: 0.000668

Gnomad4 EAS exome AF: 0.00133

Gnomad4 SAS exome AF: 0.00135

Gnomad4 FIN exome AF: 0.0000969

Gnomad4 NFE exome AF: 0.000381

Gnomad4 OTH exome AF: 0.000643

GnomAD4 genome AF: 0.000408 AC: 61 AN: 149622 Hom.: 0 Cov.: 0 AF XY: 0.000480 AC XY: 35 AN XY: 72898

Gnomad4 AFR AF: 0.000345

Gnomad4 AMR AF: 0.000199

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00158

Gnomad4 SAS AF: 0.00214

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000386

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2022	PRKCSH: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 17, 2024	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3217229; hg19: chr19-11558340;