19-11426182-C-G

Position:

• chr19-11426182-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.925G>C	p.Glu309Gln	missense_variant	7/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1	c.763G>C	p.Glu255Gln	missense_variant	7/13		NP_001289382.1
ODAD3	NM_001302454.2	c.745G>C	p.Glu249Gln	missense_variant	5/11		NP_001289383.1
ODAD3	XM_017026241.2	c.904+21G>C		intron_variant			XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.925G>C	p.Glu309Gln	missense_variant	7/13	1	NM_145045.5	ENSP00000348757	P2
ODAD3	ENST00000591179.5	c.745G>C	p.Glu249Gln	missense_variant	5/11	1		ENSP00000466800	A2
ODAD3	ENST00000586836.5	c.352G>C	p.Glu118Gln	missense_variant	7/13	2		ENSP00000467429	A2
ODAD3	ENST00000591345.5	c.*844G>C		3_prime_UTR_variant, NMD_transcript_variant	8/14	5		ENSP00000467313

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.089
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Uncertain	0.38	D
MutationAssessor	Uncertain	2.9	M;.;.
MutationTaster	Benign	0.98	D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	N;.;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.017	D;.;.
Sift4G	Uncertain	0.051	T;D;D
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs587777779; hg19: chr19-11537002;