chr19-11447525-AGAGGAGGAGGAG-A

Position:

• chr19-11447525-AGAGGAGGAGGAG-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BS1 BS2

The NM_001289104.2(PRKCSH):​c.957_968delGGAGGAGGAGGA​(p.Glu320_Glu323del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000161 in 1,583,918 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: PRKCSH NM_001289104.2 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B: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 Benign. Variant got -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001289104.2
• BP6: Variant 19-11447525-AGAGGAGGAGGAG-A is Benign according to our data. Variant chr19-11447525-AGAGGAGGAGGAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2051254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000166 (238/1434292) while in subpopulation EAS AF= 0.00228 (89/39096). AF 95% confidence interval is 0.00189. There are 1 homozygotes in gnomad4_exome. There are 121 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKCSH	NM_001289104.2	c.957_968delGGAGGAGGAGGA	p.Glu320_Glu323del	disruptive_inframe_deletion	11/18	ENST00000677123.1	NP_001276033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKCSH	ENST00000677123.1	c.957_968delGGAGGAGGAGGA	p.Glu320_Glu323del	disruptive_inframe_deletion	11/18		NM_001289104.2	ENSP00000503163.1

Frequencies

GnomAD3 genomes AF: 0.000114 AC: 17 AN: 149518 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000741

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000395

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000166 AC: 238 AN: 1434292 Hom.: 1 AF XY: 0.000170 AC XY: 121 AN XY: 712772

Gnomad4 AFR exome AF: 0.0000912

Gnomad4 AMR exome AF: 0.0000952

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00228

Gnomad4 SAS exome AF: 0.000178

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000987

Gnomad4 OTH exome AF: 0.000236

GnomAD4 genome AF: 0.000114 AC: 17 AN: 149626 Hom.: 0 Cov.: 0 AF XY: 0.0000686 AC XY: 5 AN XY: 72902

Gnomad4 AFR AF: 0.0000739

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000396

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000163

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 07, 2023

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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;