rs370978492

chr19-11430890-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.505

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 -10 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 ClinVar 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 male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_145045.5	c.366+9C>T		intron_variant		ENST00000356392.9
ODAD3	NM_001302453.1	c.204+9C>T		intron_variant
ODAD3	NM_001302454.2	c.366+9C>T		intron_variant
ODAD3	XM_017026241.2	c.366+9C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.366+9C>T		intron_variant		1	NM_145045.5	P2

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 48 AN: 152034 Hom.: 0 Cov.: 30

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

GnomAD3 exomes AF: 0.000160 AC: 40 AN: 249436 Hom.: 0 AF XY: 0.000177 AC XY: 24 AN XY: 135314

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 SAS 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

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000549

Gnomad4 OTH exome AF: 0.000232

GnomAD4 genome AF: 0.000316 AC: 48 AN: 152034 Hom.: 0 Cov.: 30 AF XY: 0.000229 AC XY: 17 AN XY: 74264

Gnomad4 AFR AF: 0.0000967

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.00

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

Submissions by phenotype

Primary ciliary dyskinesia 30 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Sep 15, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.065
Dann	Benign	0.66

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: rs370978492; hg19: chr19-11541710;