19-11435484-CCTCT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000591946.5(PRKCSH):c.-297_-294del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 380,450 control chromosomes in the GnomAD database, including 186 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (150 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (36 hom.)
• Consequence: PRKCSH ENST00000591946.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00200

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]

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-11435484-CCTCT-C is Benign according to our data. Variant chr19-11435484-CCTCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 328162.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_001302453.1	c.82+202_82+205del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKCSH	ENST00000591946.5	c.-297_-294del		5_prime_UTR_variant	1/3	2
ODAD3	ENST00000586836.5	c.-330+202_-330+205del		intron_variant		2		A2
PRKCSH	ENST00000676823.1	c.-140+44_-140+47del		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0258 AC: 3935 AN: 152228 Hom.: 148 Cov.: 32

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.00450 AC: 1026 AN: 228104 Hom.: 36 AF XY: 0.00405 AC XY: 508 AN XY: 125504

Gnomad4 AFR exome AF: 0.0957

Gnomad4 AMR exome AF: 0.00684

Gnomad4 ASJ exome AF: 0.0127

Gnomad4 EAS exome AF: 0.00110

Gnomad4 SAS exome AF: 0.00240

Gnomad4 FIN exome AF: 0.000439

Gnomad4 NFE exome AF: 0.000907

Gnomad4 OTH exome AF: 0.00606

GnomAD4 genome AF: 0.0259 AC: 3952 AN: 152346 Hom.: 150 Cov.: 32 AF XY: 0.0246 AC XY: 1832 AN XY: 74486

Gnomad4 AFR AF: 0.0864

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0242

Alfa AF: 0.00398 Hom.: 4

Bravo AF: 0.0306

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Polycystic liver disease 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs376159338; hg19: chr19-11546305;