rs34540645

Variant names:

• chr19-48302758-C-T
• rs34540645
• NM_001364171.2:c.1176G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001364171.2(ODAD1):​c.1176G>A​(p.Ser392Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,613,612 control chromosomes in the GnomAD database, including 6,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (386 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5633 hom.)
• Consequence: ODAD1 NM_001364171.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.35

Genes affected

ODAD1 (HGNC:26560): (outer dynein arm docking complex subunit 1) This gene encodes a coiled-coil domain-containing protein that is a component of the outer dynein arm docking complex in cilia cells. Mutations in this gene may cause primary ciliary dyskinesia 20. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-48302758-C-T is Benign according to our data. Variant chr19-48302758-C-T is described in ClinVar as [Benign]. Clinvar id is 262483.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD1	NM_001364171.2	c.1176G>A	p.Ser392Ser	synonymous_variant	Exon 12 of 16	ENST00000674294.1	NP_001351100.1
ODAD1	NM_144577.4	c.1065G>A	p.Ser355Ser	synonymous_variant	Exon 10 of 14		NP_653178.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD1	ENST00000674294.1	c.1176G>A	p.Ser392Ser	synonymous_variant	Exon 12 of 16		NM_001364171.2	ENSP00000501363.1

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9146 AN: 152202 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0169

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.0669

Gnomad ASJ AF: 0.0905

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0929

Gnomad OTH AF: 0.0765

GnomAD3 exomes AF: 0.0604 AC: 15094 AN: 249964 Hom.: 632 AF XY: 0.0609 AC XY: 8238 AN XY: 135278

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.0472

Gnomad ASJ exome AF: 0.0940

Gnomad EAS exome AF: 0.000327

Gnomad SAS exome AF: 0.0239

Gnomad FIN exome AF: 0.0399

Gnomad NFE exome AF: 0.0909

Gnomad OTH exome AF: 0.0734

GnomAD4 exome AF: 0.0823 AC: 120296 AN: 1461292 Hom.: 5633 Cov.: 34 AF XY: 0.0805 AC XY: 58551 AN XY: 726974

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.0502

Gnomad4 ASJ exome AF: 0.0946

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0242

Gnomad4 FIN exome AF: 0.0412

Gnomad4 NFE exome AF: 0.0950

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.0600 AC: 9143 AN: 152320 Hom.: 386 Cov.: 32 AF XY: 0.0573 AC XY: 4269 AN XY: 74472

Gnomad4 AFR AF: 0.0168

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.0905

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0223

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0929

Gnomad4 OTH AF: 0.0757

Alfa AF: 0.0821 Hom.: 332

Bravo AF: 0.0603

Asia WGS AF: 0.0120 AC: 41 AN: 3478

EpiCase AF: 0.0966

EpiControl AF: 0.0963

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:2

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: 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	-0.78
CADD	Benign	0.12
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34540645; hg19: chr19-48806015; COSMIC: COSV59559007; COSMIC: COSV59559007;