Variant 19-11426206-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I301V) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Variant links:

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]

ODAD3 links:

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ACMG classification

Classification made for transcript

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
ODAD3	NM_145045.5 linkuse as main transcript	c.901A>T	p.Ile301Leu	missense_variant	7/13	ENST00000356392.9
ODAD3	NM_001302453.1 linkuse as main transcript	c.739A>T	p.Ile247Leu	missense_variant	7/13
ODAD3	NM_001302454.2 linkuse as main transcript	c.721A>T	p.Ile241Leu	missense_variant	5/11
ODAD3	XM_017026241.2 linkuse as main transcript	c.901A>T	p.Ile301Leu	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9 linkuse as main transcript	c.901A>T	p.Ile301Leu	missense_variant	7/13	1	NM_145045.5	P2	A5D8V7-1
ODAD3	ENST00000591179.5 linkuse as main transcript	c.721A>T	p.Ile241Leu	missense_variant	5/11	1		A2
ODAD3	ENST00000586836.5 linkuse as main transcript	c.328A>T	p.Ile110Leu	missense_variant	7/13	2		A2
ODAD3	ENST00000591345.5 linkuse as main transcript	c.*820A>T		3_prime_UTR_variant, NMD_transcript_variant	8/14	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248986

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135156

show subpopulations

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:

AN:

1461632

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727144

show subpopulations

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.:

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

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

LIST_S2

Benign

0.63

T;T;T

M_CAP

Uncertain

0.095

MetaRNN

Benign

0.039

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.64

N;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.41

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over