ENST00000852992.1:c.-299_-298delCT

Variant names:

• chr19-11435484-CCT-C
• rs376159338
• ENST00000852992.1:c.-299_-298delCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000852992.1(PRKCSH):​c.-299_-298delCT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKCSH ENST00000852992.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• Publications: 0 publications found

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]

ODAD3 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 30

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000852992.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	NM_001302453.1		c.82+204_82+205delAG		intron	N/A	NP_001289382.1	A5D8V7-2
	PRKCSH	NM_001289104.2	MANE Select	c.-299_-298delCT		upstream_gene	N/A	NP_001276033.1	K7ELL7
	PRKCSH	NM_001289103.2		c.-303_-302delCT		upstream_gene	N/A	NP_001276032.1	K7ELL7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKCSH	ENST00000852992.1		c.-299_-298delCT		5_prime_UTR	Exon 1 of 18	ENSP00000523051.1
	PRKCSH	ENST00000591946.5	TSL:2	c.-295_-294delCT		5_prime_UTR	Exon 1 of 3	ENSP00000464835.1	K7EIP3
	PRKCSH	ENST00000852989.1		c.-144+46_-144+47delCT		intron	N/A	ENSP00000523048.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 228106 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 125506

African (AFR) AF: 0.00 AC: 0 AN: 5854

American (AMR) AF: 0.00 AC: 0 AN: 12286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5052

East Asian (EAS) AF: 0.00 AC: 0 AN: 8182

South Asian (SAS) AF: 0.00 AC: 0 AN: 44974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 131160

Other (OTH) AF: 0.00 AC: 0 AN: 10728

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 4

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0020

Splicing

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

Other links and lift over

dbSNP: rs376159338; hg19: chr19-11546305;