19-11420951-A-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_145045.5(ODAD3):c.1676-4T>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.00064 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ODAD3 NM_145045.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0008934
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-11420951-A-C is Benign according to our data. Variant chr19-11420951-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 738040.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_145045.5	c.1676-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000356392.9
ODAD3	NM_001302453.1	c.1514-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
ODAD3	NM_001302454.2	c.1496-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.1676-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145045.5	P2
ODAD3	ENST00000591179.5	c.1496-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		A2
ODAD3	ENST00000586836.5	c.1103-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		A2
ODAD3	ENST00000591345.5	c.*1595-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000642 AC: 781 AN: 1215906 Hom.: 0 Cov.: 30 AF XY: 0.000605 AC XY: 371 AN XY: 613186

Gnomad4 AFR exome AF: 0.000420

Gnomad4 AMR exome AF: 0.0000451

Gnomad4 ASJ exome AF: 0.000367

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.000233

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000794

Gnomad4 OTH exome AF: 0.000499

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.7
Dann	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00089
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.020		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;