19-11420951-A-T

Variant names:

• chr19-11420951-A-T
• rs772883830
• NM_145045.5:c.1676-4T>A

Variant summary

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

The NM_145045.5(ODAD3):​c.1676-4T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,216,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: ODAD3 NM_145045.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003011
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

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=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ODAD3	NM_145045.5	c.1676-4T>A		splice_region_variant, intron_variant	Intron 12 of 12	ENST00000356392.9	NP_659482.3
ODAD3	NM_001302453.1	c.1514-4T>A		splice_region_variant, intron_variant	Intron 12 of 12		NP_001289382.1
ODAD3	NM_001302454.2	c.1496-4T>A		splice_region_variant, 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.1676-4T>A		splice_region_variant, intron_variant	Intron 12 of 12	1	NM_145045.5	ENSP00000348757.3
ODAD3	ENST00000591179.5	c.1496-4T>A		splice_region_variant, intron_variant	Intron 10 of 10	1		ENSP00000466800.1
ODAD3	ENST00000586836.5	c.1103-4T>A		splice_region_variant, intron_variant	Intron 12 of 12	2		ENSP00000467429.1
ODAD3	ENST00000591345.5	n.*1595-4T>A		splice_region_variant, intron_variant	Intron 13 of 13	5		ENSP00000467313.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247798 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134718

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000895

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000255 AC: 31 AN: 1216172 Hom.: 0 Cov.: 30 AF XY: 0.0000196 AC XY: 12 AN XY: 613294

Gnomad4 AFR exome AF: 0.0000700

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000245

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000292

Gnomad4 OTH exome AF: 0.0000192

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000030
dbscSNV1_RF	Benign	0.0080
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: rs772883830; hg19: chr19-11531619;