19-11426185-C-G

Position:

• chr19-11426185-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145045.5(ODAD3):​c.922G>C​(p.Ala308Pro) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A308T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.29

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	UniProt
ODAD3	NM_145045.5	c.922G>C	p.Ala308Pro	missense_variant	7/13	ENST00000356392.9
ODAD3	NM_001302453.1	c.760G>C	p.Ala254Pro	missense_variant	7/13
ODAD3	NM_001302454.2	c.742G>C	p.Ala248Pro	missense_variant	5/11
ODAD3	XM_017026241.2	c.904+18G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.922G>C	p.Ala308Pro	missense_variant	7/13	1	NM_145045.5	P2
ODAD3	ENST00000591179.5	c.742G>C	p.Ala248Pro	missense_variant	5/11	1		A2
ODAD3	ENST00000586836.5	c.349G>C	p.Ala117Pro	missense_variant	7/13	2		A2
ODAD3	ENST00000591345.5	c.*841G>C		3_prime_UTR_variant, NMD_transcript_variant	8/14	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.097
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.54	D;D;D
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Uncertain	2.7	M;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-4.0	D;.;.
REVEL	Uncertain	0.38
Sift	Uncertain	0.0080	D;.;.
Sift4G	Benign	0.13	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.52
MutPred		0.17		Gain of glycosylation at A308 (P = 0.0076);.;.;
MVP		0.88
MPC		1.5
ClinPred		0.98	D
GERP RS		3.4
Varity_R		0.81
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201899388; hg19: chr19-11537005;