rs370978492

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_145045.5(ODAD3):​c.366+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000418 in 1,613,840 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00043 ( 2 hom. )

Consequence

ODAD3
NM_145045.5 intron

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.505

Publications

1 publications found
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 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
Variant 19-11430890-G-A is Benign according to our data. Variant chr19-11430890-G-A is described in CliVar as Likely_benign. Clinvar id is 477981.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11430890-G-A is described in CliVar as Likely_benign. Clinvar id is 477981.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11430890-G-A is described in CliVar as Likely_benign. Clinvar id is 477981.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11430890-G-A is described in CliVar as Likely_benign. Clinvar id is 477981.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11430890-G-A is described in CliVar as Likely_benign. Clinvar id is 477981.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11430890-G-A is described in CliVar as Likely_benign. Clinvar id is 477981.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-11430890-G-A is described in CliVar as Likely_benign. Clinvar id is 477981.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000316 (48/152034) while in subpopulation NFE AF = 0.000632 (43/68018). AF 95% confidence interval is 0.000482. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ODAD3NM_145045.5 linkc.366+9C>T intron_variant Intron 2 of 12 ENST00000356392.9 NP_659482.3 A5D8V7-1B3KPH7
ODAD3NM_001302453.1 linkc.204+9C>T intron_variant Intron 2 of 12 NP_001289382.1 A5D8V7-2
ODAD3NM_001302454.2 linkc.366+9C>T intron_variant Intron 2 of 10 NP_001289383.1 K7EN59
ODAD3XM_017026241.2 linkc.366+9C>T intron_variant Intron 2 of 8 XP_016881730.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ODAD3ENST00000356392.9 linkc.366+9C>T intron_variant Intron 2 of 12 1 NM_145045.5 ENSP00000348757.3 A5D8V7-1

Frequencies

GnomAD3 genomes
AF:
0.000316
AC:
48
AN:
152034
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000967
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000632
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000160
AC:
40
AN:
249436
AF XY:
0.000177
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000318
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000429
AC:
627
AN:
1461806
Hom.:
2
Cov.:
35
AF XY:
0.000422
AC XY:
307
AN XY:
727188
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33480
American (AMR)
AF:
0.0000447
AC:
2
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.000549
AC:
610
AN:
1111950
Other (OTH)
AF:
0.000232
AC:
14
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.489
Heterozygous variant carriers
0
34
69
103
138
172
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
28
56
84
112
140
<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:
0.000316
AC:
48
AN:
152034
Hom.:
0
Cov.:
30
AF XY:
0.000229
AC XY:
17
AN XY:
74264
show subpopulations
African (AFR)
AF:
0.0000967
AC:
4
AN:
41378
American (AMR)
AF:
0.0000656
AC:
1
AN:
15244
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10594
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000632
AC:
43
AN:
68018
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.481
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.000366
Hom.:
0
Bravo
AF:
0.000306
EpiCase
AF:
0.000273
EpiControl
AF:
0.000296

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 30 Benign:1
Aug 28, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.065
DANN
Benign
0.66
PhyloP100
-0.51
Mutation Taster
=100/0
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

Other links and lift over

dbSNP: rs370978492; hg19: chr19-11541710; API