Variant 19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAGGAGGAGGAGGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP3BS1_SupportingBS2

The NM_001289104.2(PRKCSH):c.963_968dup(p.Glu324_Glu325dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T312T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

PRKCSH
NM_001289104.2 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Variant links:

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]

PRKCSH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001289104.2

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000742 (111/149626) while in subpopulation AFR AF= 0.00214 (87/40622). AF 95% confidence interval is 0.00178. There are 0 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 111 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2 linkuse as main transcript	c.963_968dup	p.Glu324_Glu325dup	inframe_insertion	11/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1 linkuse as main transcript	c.963_968dup	p.Glu324_Glu325dup	inframe_insertion	11/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes

AF:

0.000742

AC:

111

AN:

149518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000398

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00107

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000163

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000308

AC:

AN:

175324

Hom.:

AF XY:

0.000220

AC XY:

AN XY:

95328

show subpopulations

Gnomad AFR exome

AF:

0.00147

Gnomad AMR exome

AF:

0.000335

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000496

Gnomad SAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.000252

Gnomad NFE exome

AF:

0.000163

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.000229

AC:

328

AN:

1434296

Hom.:

Cov.:

AF XY:

0.000222

AC XY:

158

AN XY:

712774

show subpopulations

Gnomad4 AFR exome

AF:

0.00195

Gnomad4 AMR exome

AF:

0.000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.000321

Gnomad4 FIN exome

AF:

0.000174

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.000253

GnomAD4 genome

AF:

0.000742

AC:

111

AN:

149626

Hom.:

Cov.:

AF XY:

0.000782

AC XY:

AN XY:

72902

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.000398

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000396

Gnomad4 SAS

AF:

0.00107

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000163

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2023

This variant, c.963_968dup, results in the insertion of 2 amino acid(s) of the PRKCSH protein (p.Glu324_Glu325dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over