Variant 19-11422576-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_145045.5(ODAD3):c.1329G>A(p.Arg443=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,592,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

ODAD3
NM_145045.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.556

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 19-11422576-C-T is Benign according to our data. Variant chr19-11422576-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414139.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.556 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000419 (604/1439896) while in subpopulation NFE AF= 0.00052 (574/1103796). AF 95% confidence interval is 0.000485. There are 0 homozygotes in gnomad4_exome. There are 271 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ODAD3	NM_145045.5 linkuse as main transcript	c.1329G>A	p.Arg443=	synonymous_variant	10/13	ENST00000356392.9
ODAD3	NM_001302453.1 linkuse as main transcript	c.1167G>A	p.Arg389=	synonymous_variant	10/13
ODAD3	NM_001302454.2 linkuse as main transcript	c.1149G>A	p.Arg383=	synonymous_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9 linkuse as main transcript	c.1329G>A	p.Arg443=	synonymous_variant	10/13	1	NM_145045.5	P2	A5D8V7-1
ODAD3	ENST00000591179.5 linkuse as main transcript	c.1149G>A	p.Arg383=	synonymous_variant	8/11	1		A2
ODAD3	ENST00000586836.5 linkuse as main transcript	c.756G>A	p.Arg252=	synonymous_variant	10/13	2		A2
ODAD3	ENST00000591345.5 linkuse as main transcript	c.*1248G>A		3_prime_UTR_variant, NMD_transcript_variant	11/14	5

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000169

AC:

AN:

207348

Hom.:

AF XY:

0.000185

AC XY:

AN XY:

113246

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:

0.000433

Gnomad NFE exome

AF:

0.000283

Gnomad OTH exome

AF:

0.000384

GnomAD4 exome

AF:

0.000419

AC:

604

AN:

1439896

Hom.:

Cov.:

AF XY:

0.000379

AC XY:

271

AN XY:

714850

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:

0.000227

Gnomad4 NFE exome

AF:

0.000520

Gnomad4 OTH exome

AF:

0.000319

GnomAD4 genome

AF:

0.000197

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000246

Hom.:

Bravo

AF:

0.000125

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 10, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.81

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over