19-11447525-AGAGGAGGAGGAGGAGGAG-AGAG

Position:

• chr19-11447525-AGAGGAGGAGGAGGAGGAG-AGAG

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001289104.2(PRKCSH):​c.954_968del​(p.Glu321_Glu325del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,583,934 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PRKCSH NM_001289104.2 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001289104.2
• BS2: High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2	c.954_968del	p.Glu321_Glu325del	inframe_deletion	11/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1	c.954_968del	p.Glu321_Glu325del	inframe_deletion	11/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes AF: 0.000161 AC: 24 AN: 149516 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000297

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000151 AC: 217 AN: 1434310 Hom.: 0 AF XY: 0.000146 AC XY: 104 AN XY: 712786

Gnomad4 AFR exome AF: 0.0000304

Gnomad4 AMR exome AF: 0.000119

Gnomad4 ASJ exome AF: 0.0000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000238

Gnomad4 FIN exome AF: 0.0000193

Gnomad4 NFE exome AF: 0.000179

Gnomad4 OTH exome AF: 0.000185

GnomAD4 genome AF: 0.000160 AC: 24 AN: 149624 Hom.: 0 Cov.: 0 AF XY: 0.000165 AC XY: 12 AN XY: 72900

Gnomad4 AFR AF: 0.0000492

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000297

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 22, 2023

This variant, c.954_968del, results in the deletion of 5 amino acid(s) of the PRKCSH protein (p.Glu321_Glu325del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PRKCSH-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

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;