chr19-11435484-CCTCT-C

Variant names:

• chr19-11435484-CCTCT-C
• rs376159338
• ENST00000852992.1:c.-301_-298delCTCT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001302453.1(ODAD3):​c.82+202_82+205delAGAG variant causes a intron 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: ODAD3 NM_001302453.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001302453.1. 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+202_82+205delAGAG		intron	N/A	NP_001289382.1	A5D8V7-2
	PRKCSH	NM_001289104.2	MANE Select	c.-299_-296delCTCT		upstream_gene	N/A	NP_001276033.1	K7ELL7
	PRKCSH	NM_001289103.2		c.-303_-300delCTCT		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.-301_-298delCTCT		5_prime_UTR	Exon 1 of 18	ENSP00000523051.1
	PRKCSH	ENST00000591946.5	TSL:2	c.-297_-294delCTCT		5_prime_UTR	Exon 1 of 3	ENSP00000464835.1	K7EIP3
	PRKCSH	ENST00000852989.1		c.-144+44_-144+47delCTCT		intron	N/A	ENSP00000523048.1

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

African (AFR) AF: 0.0957 AC: 560 AN: 5852

American (AMR) AF: 0.00684 AC: 84 AN: 12286

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 64 AN: 5052

East Asian (EAS) AF: 0.00110 AC: 9 AN: 8182

South Asian (SAS) AF: 0.00240 AC: 108 AN: 44974

European-Finnish (FIN) AF: 0.000439 AC: 4 AN: 9116

Middle Eastern (MID) AF: 0.0172 AC: 13 AN: 754

European-Non Finnish (NFE) AF: 0.000907 AC: 119 AN: 131160

Other (OTH) AF: 0.00606 AC: 65 AN: 10728

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

African (AFR) AF: 0.0864 AC: 3592 AN: 41574

American (AMR) AF: 0.0111 AC: 170 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5188

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68036

Other (OTH) AF: 0.0242 AC: 51 AN: 2108

Alfa AF: 0.00398 Hom.: 4

Bravo AF: 0.0306

Asia WGS AF: 0.0120 AC: 40 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Polycystic liver disease 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0020
Mutation Taster		=100/0	polymorphism (auto)

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;