rs201176850

Positions:

• chr19-11421197-C-G
• chr19-11421197-C-T

Variant summary

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

The NM_145045.5(ODAD3):​c.1606G>C​(p.Glu536Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,148 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. E536K) has been classified as Uncertain significance.

• 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: 4.02

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.1606G>C	p.Glu536Gln	missense_variant	12/13	ENST00000356392.9
ODAD3	NM_001302453.1	c.1444G>C	p.Glu482Gln	missense_variant	12/13
ODAD3	NM_001302454.2	c.1426G>C	p.Glu476Gln	missense_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.1606G>C	p.Glu536Gln	missense_variant	12/13	1	NM_145045.5	P2
ODAD3	ENST00000591179.5	c.1426G>C	p.Glu476Gln	missense_variant	10/11	1		A2
ODAD3	ENST00000586836.5	c.1033G>C	p.Glu345Gln	missense_variant	12/13	2		A2
ODAD3	ENST00000591345.5	c.*1525G>C		3_prime_UTR_variant, NMD_transcript_variant	13/14	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461148 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726766

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

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	0.23
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	T;T;.
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.61	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N;.;.
REVEL	Benign	0.24
Sift	Uncertain	0.012	D;.;.
Sift4G	Benign	0.22	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.48
MutPred		0.63		Loss of methylation at R538 (P = 0.1084);.;.;
MVP		0.72
MPC		1.3
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.46
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs201176850; hg19: chr19-11531865;