rs750661034

Positions:

• chr19-11426206-T-A
• chr19-11426206-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145045.5(ODAD3):​c.901A>T​(p.Ile301Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: -2.07

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038832515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.901A>T	p.Ile301Leu	missense_variant	7/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1	c.739A>T	p.Ile247Leu	missense_variant	7/13		NP_001289382.1
ODAD3	NM_001302454.2	c.721A>T	p.Ile241Leu	missense_variant	5/11		NP_001289383.1
ODAD3	XM_017026241.2	c.901A>T	p.Ile301Leu	missense_variant	7/9		XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.901A>T	p.Ile301Leu	missense_variant	7/13	1	NM_145045.5	ENSP00000348757	P2
ODAD3	ENST00000591179.5	c.721A>T	p.Ile241Leu	missense_variant	5/11	1		ENSP00000466800	A2
ODAD3	ENST00000586836.5	c.328A>T	p.Ile110Leu	missense_variant	7/13	2		ENSP00000467429	A2
ODAD3	ENST00000591345.5	c.*820A>T		3_prime_UTR_variant, NMD_transcript_variant	8/14	5		ENSP00000467313

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248986 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135156

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461632 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727144

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

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	0.079
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.082
DANN	Benign	0.72
DEOGEN2	Benign	0.0030	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.64	N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.81	N;.;.
REVEL	Benign	0.20
Sift	Benign	1.0	T;.;.
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.23
MutPred		0.15		Loss of methylation at K306 (P = 0.0502);.;.;
MVP		0.47
MPC		0.44
ClinPred		0.069	T
GERP RS		-4.7
Varity_R		0.054
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs750661034; hg19: chr19-11537026;