19-11421133-A-T

Variant names:

• chr19-11421133-A-T
• rs76283128
• NM_145045.5:c.1670T>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145045.5(ODAD3):​c.1670T>A​(p.Phe557Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F557C) 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: 1.13

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10023537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.1670T>A	p.Phe557Tyr	missense_variant	Exon 12 of 13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1	c.1508T>A	p.Phe503Tyr	missense_variant	Exon 12 of 13		NP_001289382.1
ODAD3	NM_001302454.2	c.1490T>A	p.Phe497Tyr	missense_variant	Exon 10 of 11		NP_001289383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.1670T>A	p.Phe557Tyr	missense_variant	Exon 12 of 13	1	NM_145045.5	ENSP00000348757.3

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	Benign	0.062
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.0046	T;T;.
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.27	N;.;.
REVEL	Benign	0.036
Sift	Benign	0.46	T;.;.
Sift4G	Benign	0.28	T;T;T
Polyphen		0.0080	B;.;.
Vest4		0.31
MutPred		0.36		Gain of phosphorylation at F557 (P = 0.0108);.;.;
MVP		0.33
MPC		0.54
ClinPred		0.17	T
GERP RS		2.2
Varity_R		0.11
gMVP		0.071

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: rs76283128; hg19: chr19-11531801;