rs34091

Variant names:

• chr19-11431541-T-A
• rs34091
• NM_145045.5:c.245-521A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-11431541-T-A
• chr19-11431541-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145045.5(ODAD3):​c.245-521A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 151,234 control chromosomes in the GnomAD database, including 2,705 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2705 hom., cov: 28)
• Consequence: ODAD3 NM_145045.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.245-521A>T		intron_variant	Intron 1 of 12	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1	c.83-521A>T		intron_variant	Intron 1 of 12		NP_001289382.1
ODAD3	NM_001302454.2	c.245-521A>T		intron_variant	Intron 1 of 10		NP_001289383.1
ODAD3	XM_017026241.2	c.245-521A>T		intron_variant	Intron 1 of 8		XP_016881730.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.245-521A>T		intron_variant	Intron 1 of 12	1	NM_145045.5	ENSP00000348757.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23499 AN: 151118 Hom.: 2692 Cov.: 28

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0972

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.150

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23557 AN: 151234 Hom.: 2705 Cov.: 28 AF XY: 0.156 AC XY: 11501 AN XY: 73840

African (AFR) AF: 0.317 AC: 13062 AN: 41144

American (AMR) AF: 0.167 AC: 2524 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.0972 AC: 337 AN: 3468

East Asian (EAS) AF: 0.149 AC: 750 AN: 5048

South Asian (SAS) AF: 0.0710 AC: 340 AN: 4792

European-Finnish (FIN) AF: 0.113 AC: 1180 AN: 10468

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0705 AC: 4784 AN: 67864

Other (OTH) AF: 0.149 AC: 313 AN: 2102

Alfa AF: 0.116 Hom.: 208

Bravo AF: 0.170

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
PhyloP100		-0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34091; hg19: chr19-11542361;