Variant chr19-11435780-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001289104.2(PRKCSH):c.-78+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,401,298 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

PRKCSH
NM_001289104.2 intron

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.702

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 19-11435780-G-A is Benign according to our data. Variant chr19-11435780-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3040071.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00107 (1336/1249064) while in subpopulation NFE AF= 0.00121 (1201/994414). AF 95% confidence interval is 0.00115. There are 1 homozygotes in gnomad4_exome. There are 615 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKCSH	NM_001289104.2 linkuse as main transcript	c.-78+74G>A		intron_variant		ENST00000677123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000677123.1 linkuse as main transcript	c.-78+74G>A		intron_variant			NM_001289104.2	A2

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000867

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000644

AC:

AN:

124152

Hom.:

AF XY:

0.000617

AC XY:

AN XY:

68088

show subpopulations

Gnomad AFR exome

AF:

0.000166

Gnomad AMR exome

AF:

0.000223

Gnomad ASJ exome

AF:

0.00250

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00112

Gnomad OTH exome

AF:

0.000527

GnomAD4 exome

AF:

0.00107

AC:

1336

AN:

1249064

Hom.:

Cov.:

AF XY:

0.00100

AC XY:

615

AN XY:

613542

show subpopulations

Gnomad4 AFR exome

AF:

0.0000353

Gnomad4 AMR exome

AF:

0.000267

Gnomad4 ASJ exome

AF:

0.00251

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000144

Gnomad4 NFE exome

AF:

0.00121

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.000552

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000867

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000940

Hom.:

Bravo

AF:

0.000563

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ODAD3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 29, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.73

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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