rs11879596

Positions:

• chr19-11426557-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_145045.5(ODAD3):​c.729C>T​(p.Asn243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,614,060 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (17 hom., cov: 31)
  • Exomes 𝑓: 0.014 (160 hom.)
• Consequence: ODAD3 NM_145045.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.162

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-11426557-G-A is Benign according to our data. Variant chr19-11426557-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.162 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0115 (1747/152218) while in subpopulation NFE AF= 0.0163 (1107/67996). AF 95% confidence interval is 0.0155. There are 17 homozygotes in gnomad4. There are 824 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_145045.5	c.729C>T	p.Asn243=	synonymous_variant	6/13	ENST00000356392.9
ODAD3	NM_001302453.1	c.567C>T	p.Asn189=	synonymous_variant	6/13
ODAD3	NM_001302454.2	c.549C>T	p.Asn183=	synonymous_variant	4/11
ODAD3	XM_017026241.2	c.729C>T	p.Asn243=	synonymous_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.729C>T	p.Asn243=	synonymous_variant	6/13	1	NM_145045.5	P2
ODAD3	ENST00000591179.5	c.549C>T	p.Asn183=	synonymous_variant	4/11	1		A2
ODAD3	ENST00000586836.5	c.156C>T	p.Asn52=	synonymous_variant	6/13	2		A2
ODAD3	ENST00000591345.5	c.*648C>T		3_prime_UTR_variant, NMD_transcript_variant	7/14	5

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1743 AN: 152100 Hom.: 17 Cov.: 31

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.00852

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00973

Gnomad FIN AF: 0.0242

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0123 AC: 3061 AN: 249360 Hom.: 20 AF XY: 0.0128 AC XY: 1732 AN XY: 135300

Gnomad AFR exome AF: 0.00194

Gnomad AMR exome AF: 0.00606

Gnomad ASJ exome AF: 0.00647

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.0158

Gnomad OTH exome AF: 0.0154

GnomAD4 exome AF: 0.0140 AC: 20503 AN: 1461842 Hom.: 160 Cov.: 33 AF XY: 0.0141 AC XY: 10268 AN XY: 727224

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.00644

Gnomad4 ASJ exome AF: 0.00670

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.0151

Gnomad4 OTH exome AF: 0.0136

GnomAD4 genome AF: 0.0115 AC: 1747 AN: 152218 Hom.: 17 Cov.: 31 AF XY: 0.0111 AC XY: 824 AN XY: 74420

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00851

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0101

Gnomad4 FIN AF: 0.0242

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0142 Hom.: 26

Bravo AF: 0.0102

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0167

EpiControl AF: 0.0163

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 30 Benign:2

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.1
DANN	Benign	0.56

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

Other links and lift over

dbSNP: rs11879596; hg19: chr19-11537377; COSMIC: COSV62699599; COSMIC: COSV62699599;