Variant 19-11435654-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001289104.2(PRKCSH):c.-130C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00936 in 1,286,194 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0074 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0096 ( 65 hom. )

Consequence

PRKCSH
NM_001289104.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.145

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:

ODAD3 (HGNC:28303): (outer dynein arm docking complex subunit 3) This gene encodes a protein containing coiled-coil domains. The encoded protein functions in outer dynein arm assembly and is required for motile cilia function. Mutations in this gene result in primary ciliary dyskinesia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2014]

ODAD3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 19-11435654-C-T is Benign according to our data. Variant chr19-11435654-C-T is described in ClinVar as [Benign]. Clinvar id is 328166.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00736 (1121/152296) while in subpopulation NFE AF= 0.0107 (729/68026). AF 95% confidence interval is 0.0101. There are 11 homozygotes in gnomad4. There are 537 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1121 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2 linkuse as main transcript	c.-130C>T		5_prime_UTR_variant	1/18	ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1 linkuse as main transcript	c.-130C>T		5_prime_UTR_variant	1/18		NM_001289104.2	A2

Frequencies

GnomAD3 genomes

AF:

0.00736

AC:

1120

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.00786

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00792

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00643

AC:

838

AN:

130294

Hom.:

AF XY:

0.00608

AC XY:

432

AN XY:

71078

show subpopulations

Gnomad AFR exome

AF:

0.00230

Gnomad AMR exome

AF:

0.00505

Gnomad ASJ exome

AF:

0.00593

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00156

Gnomad FIN exome

AF:

0.00762

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.00963

AC:

10922

AN:

1133898

Hom.:

Cov.:

AF XY:

0.00933

AC XY:

5196

AN XY:

557024

show subpopulations

Gnomad4 AFR exome

AF:

0.00163

Gnomad4 AMR exome

AF:

0.00531

Gnomad4 ASJ exome

AF:

0.00565

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.0103

Gnomad4 NFE exome

AF:

0.0109

Gnomad4 OTH exome

AF:

0.00810

GnomAD4 genome

AF:

0.00736

AC:

1121

AN:

152296

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

537

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00785

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00792

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00589

Hom.:

Bravo

AF:

0.00774

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Polycystic liver disease 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.5

DANN

Benign

0.92

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