Variant 19-11435448-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000676823.1(PRKCSH):c.-140+5G>A variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 359,886 control chromosomes in the GnomAD database, including 723 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 305 hom., cov: 33)

Exomes 𝑓: 0.057 ( 418 hom. )

Consequence

PRKCSH
ENST00000676823.1 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.0008653

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.395

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 19-11435448-G-A is Benign according to our data. Variant chr19-11435448-G-A is described in ClinVar as [Benign]. Clinvar id is 328161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_001302453.1 linkuse as main transcript	c.82+242C>T		intron_variant			NP_001289382.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	Appris
PRKCSH	ENST00000591946.5 linkuse as main transcript	c.-336G>A	5_prime_UTR_variant	1/3	2	ENSP00000464835
ODAD3	ENST00000586836.5 linkuse as main transcript	c.-330+242C>T	intron_variant		2	ENSP00000467429	A2
PRKCSH	ENST00000676823.1 linkuse as main transcript	c.-140+5G>A	splice_donor_5th_base_variant, intron_variant			ENSP00000503072

Frequencies

GnomAD3 genomes

AF:

0.0518

AC:

7879

AN:

152146

Hom.:

305

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0140

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.0862

Gnomad EAS

AF:

0.0237

Gnomad SAS

AF:

0.0401

Gnomad FIN

AF:

0.0473

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0656

GnomAD4 exome

AF:

0.0571

AC:

11853

AN:

207622

Hom.:

418

Cov.:

AF XY:

0.0567

AC XY:

6395

AN XY:

112706

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.0897

Gnomad4 EAS exome

AF:

0.0293

Gnomad4 SAS exome

AF:

0.0524

Gnomad4 FIN exome

AF:

0.0518

Gnomad4 NFE exome

AF:

0.0552

Gnomad4 OTH exome

AF:

0.0576

GnomAD4 genome

AF:

0.0518

AC:

7889

AN:

152264

Hom.:

305

Cov.:

AF XY:

0.0521

AC XY:

3881

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0140

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.0862

Gnomad4 EAS

AF:

0.0237

Gnomad4 SAS

AF:

0.0408

Gnomad4 FIN

AF:

0.0473

Gnomad4 NFE

AF:

0.0582

Gnomad4 OTH

AF:

0.0649

Alfa

AF:

0.0556

Hom.:

411

Bravo

AF:

0.0581

Asia WGS

AF:

0.0450

AC:

158

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Polycystic liver disease 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00087

dbscSNV1_RF

Benign

0.11

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