rs77133587

chr19-11421766-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145045.5(ODAD3):c.1501G>A(p.Gly501Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,418 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (24 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (16 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.00500

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003677994).
• BP6: Variant 19-11421766-C-T is Benign according to our data. Variant chr19-11421766-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00847 (1290/152368) while in subpopulation AFR AF= 0.0292 (1216/41592). AF 95% confidence interval is 0.0279. There are 24 homozygotes in gnomad4. There are 606 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_145045.5	c.1501G>A	p.Gly501Ser	missense_variant	11/13	ENST00000356392.9
ODAD3	NM_001302453.1	c.1339G>A	p.Gly447Ser	missense_variant	11/13
ODAD3	NM_001302454.2	c.1321G>A	p.Gly441Ser	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.1501G>A	p.Gly501Ser	missense_variant	11/13	1	NM_145045.5	P2
ODAD3	ENST00000591179.5	c.1321G>A	p.Gly441Ser	missense_variant	9/11	1		A2
ODAD3	ENST00000586836.5	c.928G>A	p.Gly310Ser	missense_variant	11/13	2		A2
ODAD3	ENST00000591345.5	c.*1420G>A		3_prime_UTR_variant, NMD_transcript_variant	12/14	5

Frequencies

GnomAD3 genomes AF: 0.00847 AC: 1289 AN: 152250 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0293

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00194 AC: 484 AN: 248870 Hom.: 2 AF XY: 0.00149 AC XY: 202 AN XY: 135278

Gnomad AFR exome AF: 0.0286

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000784 AC: 1146 AN: 1461050 Hom.: 16 Cov.: 31 AF XY: 0.000700 AC XY: 509 AN XY: 726820

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.00107

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00199

GnomAD4 genome AF: 0.00847 AC: 1290 AN: 152368 Hom.: 24 Cov.: 32 AF XY: 0.00813 AC XY: 606 AN XY: 74500

Gnomad4 AFR AF: 0.0292

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00211 Hom.: 6

Bravo AF: 0.00938

ESP6500AA AF: 0.0274 AC: 108

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00246 AC: 297

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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

Likely benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Aug 30, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 21, 2024	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 11, 2023

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	11
Dann	Benign	0.97
DEOGEN2	Benign	0.0037	T;T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.68	T;T;T
MetaRNN	Benign	0.0037	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;.
MutationTaster	Benign	0.96	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.12	N;.;.
REVEL	Benign	0.031
Sift	Benign	0.63	T;.;.
Sift4G	Benign	0.82	T;T;T
Polyphen		0.33	B;.;.
Vest4		0.16
MVP		0.44
MPC		0.46
ClinPred		0.010	T
GERP RS		3.9
Varity_R		0.11
gMVP		0.14

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: rs77133587; hg19: chr19-11532434;