rs143295007

Positions:

• chr19-11434869-G-A

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.148C>T​(p.Pro50Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,614,184 control chromosomes in the GnomAD database, including 25 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (20 hom.)
• Consequence: ODAD3 NM_145045.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.221

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=0.003619939).
• BP6: Variant 19-11434869-G-A is Benign according to our data. Variant chr19-11434869-G-A is described in ClinVar as [Benign]. Clinvar id is 241942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00391 (595/152336) while in subpopulation AMR AF= 0.00477 (73/15308). AF 95% confidence interval is 0.00389. There are 5 homozygotes in gnomad4. There are 371 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_145045.5	c.148C>T	p.Pro50Ser	missense_variant	1/13	ENST00000356392.9
ODAD3	NM_001302454.2	c.148C>T	p.Pro50Ser	missense_variant	1/11
ODAD3	XM_017026241.2	c.148C>T	p.Pro50Ser	missense_variant	1/9
ODAD3	NM_001302453.1	c.82+821C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.148C>T	p.Pro50Ser	missense_variant	1/13	1	NM_145045.5	P2

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152218 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00477

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0231

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00335

Gnomad OTH AF: 0.00573

GnomAD3 exomes AF: 0.00429 AC: 1071 AN: 249490 Hom.: 8 AF XY: 0.00423 AC XY: 572 AN XY: 135378

Gnomad AFR exome AF: 0.000581

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000915

Gnomad FIN exome AF: 0.0210

Gnomad NFE exome AF: 0.00383

Gnomad OTH exome AF: 0.00661

GnomAD4 exome AF: 0.00358 AC: 5238 AN: 1461848 Hom.: 20 Cov.: 31 AF XY: 0.00355 AC XY: 2581 AN XY: 727226

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.00165

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.0184

Gnomad4 NFE exome AF: 0.00342

Gnomad4 OTH exome AF: 0.00323

GnomAD4 genome AF: 0.00391 AC: 595 AN: 152336 Hom.: 5 Cov.: 33 AF XY: 0.00498 AC XY: 371 AN XY: 74490

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0231

Gnomad4 NFE AF: 0.00335

Gnomad4 OTH AF: 0.00567

Alfa AF: 0.00308 Hom.: 1

Bravo AF: 0.00213

TwinsUK AF: 0.00405 AC: 15

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000760 AC: 3

ESP6500EA AF: 0.00410 AC: 34

ExAC AF: 0.00361 AC: 437

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00365

EpiControl AF: 0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 30 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 24, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.8
DANN	Benign	0.61
DEOGEN2	Benign	0.0054	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.64	T;T
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.082
Sift	Benign	0.18	T;.
Sift4G	Benign	0.71	T;T
Polyphen		0.0050	B;.
Vest4		0.14
MVP		0.13
MPC		0.46
ClinPred		0.0049	T
GERP RS		-2.5
Varity_R		0.034
gMVP		0.18

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: rs143295007; hg19: chr19-11545690; COSMIC: COSV99371195; COSMIC: COSV99371195;