19-11436202-T-TCCTCCTGTTCAC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001289104.2(PRKCSH):c.79+12_79+23dup variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,474,422 control chromosomes in the GnomAD database, including 344 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (190 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (154 hom.)
• Consequence: PRKCSH NM_001289104.2 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.947

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 -16 ACMG points.

• BP6: Variant 19-11436202-T-TCCTCCTGTTCAC is Benign according to our data. Variant chr19-11436202-T-TCCTCCTGTTCAC is described in ClinVar as [Benign]. Clinvar id is 769958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2	c.79+12_79+23dup		splice_region_variant, intron_variant		ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1	c.79+12_79+23dup		splice_region_variant, intron_variant			NM_001289104.2	A2

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 3788 AN: 143162 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0884

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000254

Gnomad OTH AF: 0.0154

GnomAD3 exomes AF: 0.00517 AC: 1046 AN: 202150 Hom.: 50 AF XY: 0.00361 AC XY: 395 AN XY: 109442

Gnomad AFR exome AF: 0.0769

Gnomad AMR exome AF: 0.00384

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000730

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000138

Gnomad OTH exome AF: 0.00189

GnomAD4 exome AF: 0.00259 AC: 3444 AN: 1331146 Hom.: 154 Cov.: 30 AF XY: 0.00214 AC XY: 1420 AN XY: 662180

Gnomad4 AFR exome AF: 0.0897

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000986

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000463

Gnomad4 OTH exome AF: 0.00542

GnomAD4 genome AF: 0.0265 AC: 3798 AN: 143276 Hom.: 190 Cov.: 32 AF XY: 0.0255 AC XY: 1779 AN XY: 69672

Gnomad4 AFR AF: 0.0884

Gnomad4 AMR AF: 0.00916

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000255

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.0204 Hom.: 8

ClinVar

Significance: 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	GeneDx	May 18, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 25, 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: rs146514973; hg19: chr19-11547023;