chr19-11434844-A-G

Variant names:

• chr19-11434844-A-G
• rs61741137
• NM_145045.5:c.173T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_145045.5(ODAD3):​c.173T>C​(p.Phe58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 1,614,158 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (5 hom., cov: 33)
  • Exomes 𝑓: 0.013 (157 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.509
• Publications: 11 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034710765).
• BP6: Variant 19-11434844-A-G is Benign according to our data. Variant chr19-11434844-A-G is described in ClinVar as Benign. ClinVar VariationId is 221005.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00737 (1122/152286) while in subpopulation NFE AF = 0.0125 (848/68012). AF 95% confidence interval is 0.0118. There are 5 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145045.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	NM_145045.5	MANE Select	c.173T>C	p.Phe58Ser	missense	Exon 1 of 13	NP_659482.3
	ODAD3	NM_001302454.2		c.173T>C	p.Phe58Ser	missense	Exon 1 of 11	NP_001289383.1
	ODAD3	NM_001302453.1		c.82+846T>C		intron	N/A	NP_001289382.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ODAD3	ENST00000356392.9	TSL:1 MANE Select	c.173T>C	p.Phe58Ser	missense	Exon 1 of 13	ENSP00000348757.3
	ODAD3	ENST00000591179.5	TSL:1	c.173T>C	p.Phe58Ser	missense	Exon 1 of 11	ENSP00000466800.1
	ODAD3	ENST00000591345.5	TSL:5	n.173T>C		non_coding_transcript_exon	Exon 1 of 14	ENSP00000467313.1

Frequencies

GnomAD3 genomes AF: 0.00738 AC: 1123 AN: 152168 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00464

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.00855 AC: 2133 AN: 249532 AF XY: 0.00892

Gnomad AFR exome AF: 0.00174

Gnomad AMR exome AF: 0.00400

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00422

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.00908

GnomAD4 exome AF: 0.0127 AC: 18553 AN: 1461872 Hom.: 157 Cov.: 31 AF XY: 0.0126 AC XY: 9151 AN XY: 727234

African (AFR) AF: 0.00170 AC: 57 AN: 33480

American (AMR) AF: 0.00463 AC: 207 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00371 AC: 97 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00788 AC: 680 AN: 86254

European-Finnish (FIN) AF: 0.00536 AC: 286 AN: 53404

Middle Eastern (MID) AF: 0.00225 AC: 13 AN: 5768

European-Non Finnish (NFE) AF: 0.0149 AC: 16585 AN: 1112010

Other (OTH) AF: 0.0103 AC: 625 AN: 60396

GnomAD4 genome AF: 0.00737 AC: 1122 AN: 152286 Hom.: 5 Cov.: 33 AF XY: 0.00658 AC XY: 490 AN XY: 74470

African (AFR) AF: 0.00245 AC: 102 AN: 41558

American (AMR) AF: 0.00464 AC: 71 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00476 AC: 23 AN: 4830

European-Finnish (FIN) AF: 0.00424 AC: 45 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0125 AC: 848 AN: 68012

Other (OTH) AF: 0.00757 AC: 16 AN: 2114

Alfa AF: 0.0115 Hom.: 8

Bravo AF: 0.00776

TwinsUK AF: 0.0148 AC: 55

ALSPAC AF: 0.0153 AC: 59

ESP6500AA AF: 0.00204 AC: 8

ESP6500EA AF: 0.0122 AC: 101

ExAC AF: 0.00902 AC: 1090

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0117

EpiControl AF: 0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ODAD3: BP4, BS1, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 16, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Primary ciliary dyskinesia 30 Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Oct 13, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.51
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0035	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.51
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.0020
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		0.0020	B
Vest4		0.097
MVP		0.12
MPC		0.89
ClinPred		0.00039	T
GERP RS		-1.6
PromoterAI		0.017	Neutral
Varity_R		0.043
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs61741137; hg19: chr19-11545665; COSMIC: COSV99372086; COSMIC: COSV99372086;