rs61742088

Positions:

• chr19-11434872-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000356392.9(ODAD3):​c.145A>C​(p.Thr49Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,614,098 control chromosomes in the GnomAD database, including 338 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 0.025 (150 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (188 hom.)
• Consequence: ODAD3 ENST00000356392.9 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.131

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=0.00212273).
• BP6: Variant 19-11434872-T-G is Benign according to our data. Variant chr19-11434872-T-G is described in ClinVar as [Benign]. Clinvar id is 414144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.145A>C	p.Thr49Pro	missense_variant	1/13	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302454.2	c.145A>C	p.Thr49Pro	missense_variant	1/11		NP_001289383.1
ODAD3	XM_017026241.2	c.145A>C	p.Thr49Pro	missense_variant	1/9		XP_016881730.1
ODAD3	NM_001302453.1	c.82+818A>C		intron_variant			NP_001289382.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.145A>C	p.Thr49Pro	missense_variant	1/13	1	NM_145045.5	ENSP00000348757	P2

Frequencies

GnomAD3 genomes AF: 0.0251 AC: 3824 AN: 152122 Hom.: 148 Cov.: 33

Gnomad AFR AF: 0.0869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00989

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.00646 AC: 1611 AN: 249490 Hom.: 72 AF XY: 0.00493 AC XY: 668 AN XY: 135372

Gnomad AFR exome AF: 0.0885

Gnomad AMR exome AF: 0.00460

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.000389

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000362

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00278 AC: 4070 AN: 1461856 Hom.: 188 Cov.: 31 AF XY: 0.00243 AC XY: 1770 AN XY: 727224

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.00519

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.000313

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.000202

Gnomad4 OTH exome AF: 0.00647

GnomAD4 genome AF: 0.0252 AC: 3844 AN: 152242 Hom.: 150 Cov.: 33 AF XY: 0.0240 AC XY: 1789 AN XY: 74452

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.00988

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0119 Hom.: 36

Bravo AF: 0.0296

ESP6500AA AF: 0.0745 AC: 294

ESP6500EA AF: 0.000241 AC: 2

ExAC AF: 0.00757 AC: 915

Asia WGS AF: 0.0110 AC: 38 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Primary ciliary dyskinesia 30 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.29
DANN	Benign	0.61
DEOGEN2	Benign	0.00066	T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.096	T;T
MetaRNN	Benign	0.0021	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-1.1	N;.
MutationTaster	Benign	1.0	D;D;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.47	N;.
REVEL	Benign	0.016
Sift	Benign	0.92	T;.
Sift4G	Benign	0.65	T;T
Polyphen		0.0	B;.
Vest4		0.14
MVP		0.072
MPC		0.58
ClinPred		0.0060	T
GERP RS		-0.50
Varity_R		0.066
gMVP		0.092

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: rs61742088; hg19: chr19-11545693; COSMIC: COSV105005770; COSMIC: COSV105005770;