19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAG

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_001289104.2(PRKCSH):c.963_968del(p.Glu324_Glu325del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0868 in 1,471,316 control chromosomes in the GnomAD database, including 1,983 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (329 hom., cov: 0)
  • Exomes 𝑓: 0.089 (1654 hom.)
• Consequence: PRKCSH NM_001289104.2 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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-AGAGGAG-A is Benign according to our data. Variant chr19-11447525-AGAGGAG-A is described in ClinVar as [Benign]. Clinvar id is 94080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11447525-AGAGGAG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2	c.963_968del	p.Glu324_Glu325del	inframe_deletion	11/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1	c.963_968del	p.Glu324_Glu325del	inframe_deletion	11/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9579 AN: 149226 Hom.: 329 Cov.: 0

Gnomad AFR AF: 0.0289

Gnomad AMI AF: 0.0337

Gnomad AMR AF: 0.0765

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.00573

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.0581

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0923

GnomAD3 exomes AF: 0.0881 AC: 15453 AN: 175324 Hom.: 186 AF XY: 0.0906 AC XY: 8640 AN XY: 95328

Gnomad AFR exome AF: 0.0506

Gnomad AMR exome AF: 0.0787

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0140

Gnomad SAS exome AF: 0.0621

Gnomad FIN exome AF: 0.0706

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0894 AC: 118178 AN: 1321984 Hom.: 1654 AF XY: 0.0888 AC XY: 58245 AN XY: 655686

Gnomad4 AFR exome AF: 0.0369

Gnomad4 AMR exome AF: 0.0727

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.00534

Gnomad4 SAS exome AF: 0.0517

Gnomad4 FIN exome AF: 0.0663

Gnomad4 NFE exome AF: 0.0978

Gnomad4 OTH exome AF: 0.0859

GnomAD4 genome AF: 0.0642 AC: 9581 AN: 149332 Hom.: 329 Cov.: 0 AF XY: 0.0626 AC XY: 4554 AN XY: 72718

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.0764

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.00574

Gnomad4 SAS AF: 0.0349

Gnomad4 FIN AF: 0.0581

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.0918

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2019	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jun 01, 2015

- -

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;