chr19-11421116-A-C

Variant names:

• chr19-11421116-A-C
• rs757027245
• NM_145045.5:c.1675+12T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145045.5(ODAD3):​c.1675+12T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000708 in 141,214 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000071 (0 hom., cov: 31)
• Consequence: ODAD3 NM_145045.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.1675+12T>G		intron_variant	Intron 12 of 12	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1	c.1513+12T>G		intron_variant	Intron 12 of 12		NP_001289382.1
ODAD3	NM_001302454.2	c.1495+12T>G		intron_variant	Intron 10 of 10		NP_001289383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ODAD3	ENST00000356392.9	c.1675+12T>G		intron_variant	Intron 12 of 12	1	NM_145045.5	ENSP00000348757.3
ODAD3	ENST00000591179.5	c.1495+12T>G		intron_variant	Intron 10 of 10	1		ENSP00000466800.1
ODAD3	ENST00000586836.5	c.1102+12T>G		intron_variant	Intron 12 of 12	2		ENSP00000467429.1
ODAD3	ENST00000591345.5	n.*1594+12T>G		intron_variant	Intron 13 of 13	5		ENSP00000467313.1

Frequencies

GnomAD3 genomes AF: 0.00000708 AC: 1 AN: 141214 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000708 AC: 1 AN: 141214 Hom.: 0 Cov.: 31 AF XY: 0.0000146 AC XY: 1 AN XY: 68532

Gnomad4 AFR AF: 0.0000266

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.5
DANN	Benign	0.76

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: rs757027245; hg19: chr19-11531784;