Variant 19-11447525-AGAGGAGGAGGAGGAGGAG-AGAGGAGGAGGAGGAGGAGGAGGAGGAG 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.960_968dup(p.Glu323_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 0.00065 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00068 ( 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 nfe. gnomad4 allele frequency = 0.000655 (98/149626) while in subpopulation NFE AF= 0.000965 (65/67348). AF 95% confidence interval is 0.000776. There are 0 homozygotes in gnomad4. There are 44 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 98 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2 linkuse as main transcript	c.960_968dup	p.Glu323_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.960_968dup	p.Glu323_Glu325dup	inframe_insertion	11/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes

AF:

0.000655

AC:

AN:

149518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000148

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000663

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000886

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000965

Gnomad OTH

AF:

0.00246

GnomAD3 exomes

AF:

0.000473

AC:

AN:

175324

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

95328

show subpopulations

Gnomad AFR exome

AF:

0.0000983

Gnomad AMR exome

AF:

0.000585

Gnomad ASJ exome

AF:

0.000522

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000930

Gnomad FIN exome

AF:

0.000441

Gnomad NFE exome

AF:

0.000652

Gnomad OTH exome

AF:

0.000690

GnomAD4 exome

AF:

0.000679

AC:

974

AN:

1434282

Hom.:

Cov.:

AF XY:

0.000682

AC XY:

486

AN XY:

712774

show subpopulations

Gnomad4 AFR exome

AF:

0.0000912

Gnomad4 AMR exome

AF:

0.000571

Gnomad4 ASJ exome

AF:

0.000468

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000131

Gnomad4 FIN exome

AF:

0.000813

Gnomad4 NFE exome

AF:

0.000774

Gnomad4 OTH exome

AF:

0.000556

GnomAD4 genome

AF:

0.000655

AC:

AN:

149626

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

72902

show subpopulations

Gnomad4 AFR

AF:

0.000148

Gnomad4 AMR

AF:

0.000663

Gnomad4 ASJ

AF:

0.000291

Gnomad4 EAS

AF:

0.000198

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000886

Gnomad4 NFE

AF:

0.000965

Gnomad4 OTH

AF:

0.00244

Bravo

AF:

0.000548

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 27, 2023

This variant, c.960_968dup, results in the insertion of 3 amino acid(s) of the PRKCSH protein (p.Glu323_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