rs1060501309

Positions:

• chr19-11426683-C-CATT

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_145045.5(ODAD3):​c.713_714insAAT​(p.Leu237_Met238insIle) variant causes a inframe insertion, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ODAD3 NM_145045.5 inframe_insertion, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_145045.5. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ODAD3	NM_145045.5	c.713_714insAAT	p.Leu237_Met238insIle	inframe_insertion, splice_region_variant	5/13	ENST00000356392.9
ODAD3	NM_001302453.1	c.551_552insAAT	p.Leu183_Met184insIle	inframe_insertion, splice_region_variant	5/13
ODAD3	XM_017026241.2	c.713_714insAAT	p.Leu237_Met238insIle	inframe_insertion, splice_region_variant	5/9
ODAD3	NM_001302454.2	c.535-113_535-112insAAT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ODAD3	ENST00000356392.9	c.713_714insAAT	p.Leu237_Met238insIle	inframe_insertion, splice_region_variant	5/13	1	NM_145045.5	P2
ODAD3	ENST00000591179.5	c.535-113_535-112insAAT		intron_variant		1		A2
ODAD3	ENST00000586836.5	c.140_141insAAT	p.Leu46_Met47insIle	inframe_insertion, splice_region_variant	5/13	2		A2
ODAD3	ENST00000591345.5	c.*632_*633insAAT		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	6/14	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 30 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 13, 2017

This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a CCDC151-related disease. This sequence change inserts 3 nucleotides in exon 5 of the CCDC151 mRNA (c.711_713dupAAT). This leads to the insertion of 1 amino acid residue in the CCDC151 protein (p.Leu237_Met238insIle) but otherwise preserves the integrity of the reading frame. In summary, this is a novel in-frame insertion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the inserted amino acid is currently unknown. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1060501309; hg19: chr19-11537503;