Genetic Variant NM_145045.5:c.366+34T>C (chr19-11430865-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_145045.5(ODAD3):c.366+34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,613,518 control chromosomes in the GnomAD database, including 244,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.62 ( 30156 hom., cov: 30)

Exomes 𝑓: 0.54 ( 214284 hom. )

Consequence

ODAD3
NM_145045.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.17

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 30
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ODAD3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (Cadd=0.088).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5 link	c.366+34T>C	intron_variant	Intron 2 of 12	ENST00000356392.9	NP_659482.3	A5D8V7-1B3KPH7
ODAD3	NM_001302453.1 link	c.204+34T>C	intron_variant	Intron 2 of 12		NP_001289382.1	A5D8V7-2
ODAD3	NM_001302454.2 link	c.366+34T>C	intron_variant	Intron 2 of 10		NP_001289383.1	K7EN59
ODAD3	XM_017026241.2 link	c.366+34T>C	intron_variant	Intron 2 of 8		XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9 link	c.366+34T>C		intron_variant	Intron 2 of 12	1	NM_145045.5	ENSP00000348757.3		A5D8V7-1

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93821

AN:

151802

Hom.:

30102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.811

Gnomad AMI

AF:

0.723

Gnomad AMR

AF:

0.550

Gnomad ASJ

AF:

0.572

Gnomad EAS

AF:

0.529

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.581

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.607

GnomAD4 exome

AF:

0.539

AC:

787611

AN:

1461598

Hom.:

214284

Cov.:

AF XY:

0.539

AC XY:

392227

AN XY:

727066

show subpopulations

African (AFR)

AF:

0.819

AC:

27424

AN:

33480

American (AMR)

AF:

0.547

AC:

24464

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

15025

AN:

26114

East Asian (EAS)

AF:

0.464

AC:

18437

AN:

39694

South Asian (SAS)

AF:

0.584

AC:

50340

AN:

86244

European-Finnish (FIN)

AF:

0.585

AC:

31233

AN:

53398

Middle Eastern (MID)

AF:

0.592

AC:

3415

AN:

5766

European-Non Finnish (NFE)

AF:

0.525

AC:

583281

AN:

1111806

Other (OTH)

AF:

0.563

AC:

33992

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.524

Heterozygous variant carriers

22449

44898

67347

89796

112245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.618

AC:

93935

AN:

151920

Hom.:

30156

Cov.:

AF XY:

0.617

AC XY:

45814

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.812

AC:

33659

AN:

41476

American (AMR)

AF:

0.550

AC:

8376

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.572

AC:

1982

AN:

3466

East Asian (EAS)

AF:

0.528

AC:

2718

AN:

5150

South Asian (SAS)

AF:

0.588

AC:

2832

AN:

4814

European-Finnish (FIN)

AF:

0.581

AC:

6124

AN:

10540

Middle Eastern (MID)

AF:

0.582

AC:

170

AN:

292

European-Non Finnish (NFE)

AF:

0.532

AC:

36130

AN:

67936

Other (OTH)

AF:

0.610

AC:

1285

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1723

3446

5170

6893

8616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.552

Hom.:

31906

Bravo

AF:

0.626

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

CADD

Benign

0.088

(source)

PhyloP100

-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_145045.5:c.366+34T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over