rs756389981

Positions:

• chr19-11435009-G-A
• chr19-11435009-G-C
• chr19-11435009-G-T

Variant summary

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

The ENST00000356392.9(ODAD3):​c.8C>T​(p.Ser3Phe) 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. S3C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ODAD3 ENST00000356392.9 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>T	p.Ser3Phe	missense_variant	1/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302454.2	c.8C>T	p.Ser3Phe	missense_variant	1/11		NP_001289383.1
ODAD3	XM_017026241.2	c.8C>T	p.Ser3Phe	missense_variant	1/9		XP_016881730.1
ODAD3	NM_001302453.1	c.82+681C>T		intron_variant			NP_001289382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.8C>T	p.Ser3Phe	missense_variant	1/13	1	NM_145045.5	ENSP00000348757	P2
ODAD3	ENST00000591179.5	c.8C>T	p.Ser3Phe	missense_variant	1/11	1		ENSP00000466800	A2
ODAD3	ENST00000586836.5	c.-330+681C>T		intron_variant		2		ENSP00000467429	A2
ODAD3	ENST00000591345.5	c.8C>T	p.Ser3Phe	missense_variant, NMD_transcript_variant	1/14	5		ENSP00000467313

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000375 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.0079	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0027	T;T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.60	N;.
REVEL	Benign	0.076
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.57
MVP		0.68
MPC		1.4
ClinPred		0.95	D
GERP RS		1.4
Varity_R		0.17
gMVP		0.36

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; COSMIC: COSV104577630; COSMIC: COSV104577630;