19-11430892-C-T

Variant names:

• chr19-11430892-C-T
• rs34094
• NM_145045.5:c.366+7G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145045.5(ODAD3):​c.366+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,613,976 control chromosomes in the GnomAD database, including 1,862 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.065 (807 hom., cov: 30)
  • Exomes 𝑓: 0.018 (1055 hom.)
• Consequence: ODAD3 NM_145045.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 10 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• polycystic liver disease 1

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.288).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145045.5. 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_145045.5	MANE Select	c.366+7G>A		splice_region intron	N/A	NP_659482.3
	ODAD3	NM_001302453.1		c.204+7G>A		splice_region intron	N/A	NP_001289382.1	A5D8V7-2
	ODAD3	NM_001302454.2		c.366+7G>A		splice_region intron	N/A	NP_001289383.1	K7EN59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	ENST00000356392.9	TSL:1 MANE Select	c.366+7G>A		splice_region intron	N/A	ENSP00000348757.3	A5D8V7-1
	ODAD3	ENST00000591179.5	TSL:1	c.366+7G>A		splice_region intron	N/A	ENSP00000466800.1	K7EN59
	PRKCSH	ENST00000916401.1		c.-283C>T		5_prime_UTR	Exon 4 of 22	ENSP00000586460.1

Frequencies

GnomAD3 genomes AF: 0.0651 AC: 9891 AN: 152028 Hom.: 804 Cov.: 30

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00937

Gnomad OTH AF: 0.0578

GnomAD4 exome AF: 0.0181 AC: 26460 AN: 1461830 Hom.: 1055 Cov.: 35 AF XY: 0.0180 AC XY: 13079 AN XY: 727202

African (AFR) AF: 0.186 AC: 6229 AN: 33478

American (AMR) AF: 0.0172 AC: 770 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 368 AN: 26134

East Asian (EAS) AF: 0.101 AC: 3998 AN: 39696

South Asian (SAS) AF: 0.0303 AC: 2614 AN: 86258

European-Finnish (FIN) AF: 0.0254 AC: 1359 AN: 53412

Middle Eastern (MID) AF: 0.0239 AC: 138 AN: 5768

European-Non Finnish (NFE) AF: 0.00806 AC: 8961 AN: 1111966

Other (OTH) AF: 0.0335 AC: 2023 AN: 60394

GnomAD4 genome AF: 0.0652 AC: 9918 AN: 152146 Hom.: 807 Cov.: 30 AF XY: 0.0639 AC XY: 4757 AN XY: 74398

African (AFR) AF: 0.182 AC: 7533 AN: 41482

American (AMR) AF: 0.0331 AC: 506 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.125 AC: 645 AN: 5168

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4816

European-Finnish (FIN) AF: 0.0257 AC: 273 AN: 10608

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00937 AC: 637 AN: 68008

Other (OTH) AF: 0.0581 AC: 123 AN: 2116

Alfa AF: 0.0255 Hom.: 411

Bravo AF: 0.0705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.3
PhyloP100		-0.65

Splicing

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

Other links and lift over

dbSNP: rs34094;