chr19-11426182-C-G

Variant names:

• chr19-11426182-C-G
• rs587777779
• NM_145045.5:c.925G>C

Variant summary

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

The NM_145045.5(ODAD3):​c.925G>C​(p.Glu309Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,758 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 7 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet, Genomics England PanelApp

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: 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.925G>C	p.Glu309Gln	missense	Exon 7 of 13	NP_659482.3
	ODAD3	NM_001302453.1		c.763G>C	p.Glu255Gln	missense	Exon 7 of 13	NP_001289382.1
	ODAD3	NM_001302454.2		c.745G>C	p.Glu249Gln	missense	Exon 5 of 11	NP_001289383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	ENST00000356392.9	TSL:1 MANE Select	c.925G>C	p.Glu309Gln	missense	Exon 7 of 13	ENSP00000348757.3
	ODAD3	ENST00000591179.5	TSL:1	c.745G>C	p.Glu249Gln	missense	Exon 5 of 11	ENSP00000466800.1
	ODAD3	ENST00000861507.1		c.823G>C	p.Glu275Gln	missense	Exon 6 of 12	ENSP00000531566.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460758 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726734

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52842

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111714

Other (OTH) AF: 0.00 AC: 0 AN: 60352

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.9	M
PhyloP100		2.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.33
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.051	T
Polyphen		1.0	D
Vest4		0.44
MutPred		0.15		Loss of ubiquitination at K312 (P = 0.0234)
MVP		0.82
MPC		1.3
ClinPred		0.99	D
GERP RS		3.4
Varity_R		0.28
gMVP		0.36
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs587777779; hg19: chr19-11537002;