19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAGGAGGAGGAGGAGGAGGAG

Variant names:

• chr19-11447525-A-AGAGGAGGAGGAG
• rs3217229
• NM_001289104.2:c.957_968dupGGAGGAGGAGGA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP3 BS2_Supporting

The NM_001289104.2(PRKCSH):​c.957_968dupGGAGGAGGAGGA​(p.Glu320_Glu323dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000042 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKCSH NM_001289104.2 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52

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 -2 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001289104.2
• BS2: High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCSH	NM_001289104.2	c.957_968dupGGAGGAGGAGGA	p.Glu320_Glu323dup	disruptive_inframe_insertion	Exon 11 of 18	ENST00000677123.1	NP_001276033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCSH	ENST00000677123.1	c.957_968dupGGAGGAGGAGGA	p.Glu320_Glu323dup	disruptive_inframe_insertion	Exon 11 of 18		NM_001289104.2	ENSP00000503163.1

Frequencies

GnomAD3 genomes AF: 0.0000401 AC: 6 AN: 149518 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000494

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000418 AC: 60 AN: 1434308 Hom.: 0 Cov.: 0 AF XY: 0.0000533 AC XY: 38 AN XY: 712784

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000390

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000190

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000347

Gnomad4 OTH exome AF: 0.0000843

GnomAD4 genome AF: 0.0000401 AC: 6 AN: 149518 Hom.: 0 Cov.: 0 AF XY: 0.0000550 AC XY: 4 AN XY: 72784

Gnomad4 AFR AF: 0.0000494

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000213

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000297

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polycystic liver disease 1 Uncertain:1

Apr 04, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;