rs61739927

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145045.5(ODAD3):​c.424C>G​(p.Leu142Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 1,614,046 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 32)
Exomes 𝑓: 0.0081 ( 64 hom. )

Consequence

ODAD3
NM_145045.5 missense

Scores

3
15

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.07
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4
Computational evidence support a benign effect (MetaRNN=0.010106593).
BP6
Variant 19-11430719-G-C is Benign according to our data. Variant chr19-11430719-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 414138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-11430719-G-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1816/152174) while in subpopulation AFR AF = 0.0233 (966/41522). AF 95% confidence interval is 0.022. There are 26 homozygotes in GnomAd4. There are 921 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
BS2
High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ODAD3NM_145045.5 linkc.424C>G p.Leu142Val missense_variant Exon 3 of 13 ENST00000356392.9 NP_659482.3 A5D8V7-1B3KPH7
ODAD3NM_001302453.1 linkc.262C>G p.Leu88Val missense_variant Exon 3 of 13 NP_001289382.1 A5D8V7-2
ODAD3XM_017026241.2 linkc.424C>G p.Leu142Val missense_variant Exon 3 of 9 XP_016881730.1
ODAD3NM_001302454.2 linkc.366+180C>G intron_variant Intron 2 of 10 NP_001289383.1 K7EN59

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ODAD3ENST00000356392.9 linkc.424C>G p.Leu142Val missense_variant Exon 3 of 13 1 NM_145045.5 ENSP00000348757.3 A5D8V7-1

Frequencies

GnomAD3 genomes
AF:
0.0118
AC:
1787
AN:
152056
Hom.:
23
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0228
Gnomad AMI
AF:
0.0451
Gnomad AMR
AF:
0.00525
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00792
Gnomad SAS
AF:
0.0131
Gnomad FIN
AF:
0.00735
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00772
Gnomad OTH
AF:
0.00718
GnomAD2 exomes
AF:
0.00794
AC:
1981
AN:
249508
AF XY:
0.00825
show subpopulations
Gnomad AFR exome
AF:
0.0246
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.00795
Gnomad FIN exome
AF:
0.00672
Gnomad NFE exome
AF:
0.00719
Gnomad OTH exome
AF:
0.00727
GnomAD4 exome
AF:
0.00814
AC:
11900
AN:
1461872
Hom.:
64
Cov.:
31
AF XY:
0.00830
AC XY:
6038
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.0252
AC:
844
AN:
33480
Gnomad4 AMR exome
AF:
0.00284
AC:
127
AN:
44724
Gnomad4 ASJ exome
AF:
0.0000383
AC:
1
AN:
26136
Gnomad4 EAS exome
AF:
0.00411
AC:
163
AN:
39700
Gnomad4 SAS exome
AF:
0.0129
AC:
1117
AN:
86258
Gnomad4 FIN exome
AF:
0.00545
AC:
291
AN:
53420
Gnomad4 NFE exome
AF:
0.00795
AC:
8844
AN:
1111994
Gnomad4 Remaining exome
AF:
0.00778
AC:
470
AN:
60392
Heterozygous variant carriers
0
650
1301
1951
2602
3252
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
372
744
1116
1488
1860
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0119
AC:
1816
AN:
152174
Hom.:
26
Cov.:
32
AF XY:
0.0124
AC XY:
921
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.0233
AC:
0.0232648
AN:
0.0232648
Gnomad4 AMR
AF:
0.00524
AC:
0.00524315
AN:
0.00524315
Gnomad4 ASJ
AF:
0.000288
AC:
0.000288184
AN:
0.000288184
Gnomad4 EAS
AF:
0.00794
AC:
0.00793651
AN:
0.00793651
Gnomad4 SAS
AF:
0.0131
AC:
0.013076
AN:
0.013076
Gnomad4 FIN
AF:
0.00735
AC:
0.00735294
AN:
0.00735294
Gnomad4 NFE
AF:
0.00772
AC:
0.00771855
AN:
0.00771855
Gnomad4 OTH
AF:
0.00948
AC:
0.00947867
AN:
0.00947867
Heterozygous variant carriers
0
91
182
272
363
454
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Genome Hom
Variant carriers
0
26
52
78
104
130
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00812
Hom.:
1
Bravo
AF:
0.0124
TwinsUK
AF:
0.0116
AC:
43
ALSPAC
AF:
0.00545
AC:
21
ESP6500AA
AF:
0.0219
AC:
91
ESP6500EA
AF:
0.00704
AC:
59
ExAC
AF:
0.00839
AC:
1015
Asia WGS
AF:
0.0150
AC:
53
AN:
3478
EpiCase
AF:
0.00545
EpiControl
AF:
0.00741

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

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

- -

Nov 09, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:2
Apr 21, 2020
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0096
T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.31
FATHMM_MKL
Benign
0.44
N
LIST_S2
Benign
0.78
T
MetaRNN
Benign
0.010
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.34
Sift
Benign
0.11
T
Sift4G
Benign
0.29
T
Polyphen
0.95
P
Vest4
0.49
MVP
0.81
MPC
1.2
ClinPred
0.013
T
GERP RS
0.47
Varity_R
0.069
gMVP
0.18
Mutation Taster
=298/2
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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61739927; hg19: chr19-11541539; COSMIC: COSV52953573; COSMIC: COSV52953573; API