19-11435009-G-T

Position:

• chr19-11435009-G-T

Variant summary

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

The NM_145045.5(ODAD3):​c.8C>A​(p.Ser3Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,124 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12

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.8C>A	p.Ser3Tyr	missense_variant	1/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302454.2	c.8C>A	p.Ser3Tyr	missense_variant	1/11		NP_001289383.1
ODAD3	XM_017026241.2	c.8C>A	p.Ser3Tyr	missense_variant	1/9		XP_016881730.1
ODAD3	NM_001302453.1	c.82+681C>A		intron_variant			NP_001289382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.8C>A	p.Ser3Tyr	missense_variant	1/13	1	NM_145045.5	ENSP00000348757.3
ODAD3	ENST00000591179.5	c.8C>A	p.Ser3Tyr	missense_variant	1/11	1		ENSP00000466800.1
ODAD3	ENST00000586836.5	c.-330+681C>A		intron_variant		2		ENSP00000467429.1
ODAD3	ENST00000591345.5	n.8C>A		non_coding_transcript_exon_variant	1/14	5		ENSP00000467313.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000820 AC: 2 AN: 244038 Hom.: 0 AF XY: 0.00000752 AC XY: 1 AN XY: 133056

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: 0.0000180

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1458124 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725400

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0033	T;T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.81	T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.67	N;.
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.55
MutPred		0.17		Gain of catalytic residue at S3 (P = 0.0367);Gain of catalytic residue at S3 (P = 0.0367);
MVP		0.68
MPC		1.5
ClinPred		0.93	D
GERP RS		1.4
Varity_R		0.14
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs756389981; hg19: chr19-11545830;