17-80090346-A-AC

Position:

• chr17-80090346-A-AC

Variant summary

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

The NM_017950.4(CCDC40):​c.2832+462_2832+463insC variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

Genes affected

CCDC40 (HGNC:26090): (coiled-coil domain 40 molecular ruler complex subunit) This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.2832+462_2832+463insC		intron_variant		ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.3040_3041insC	p.Arg1014ThrfsTer80	frameshift_variant	18/18		NP_001230271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.2832+462_2832+463insC		intron_variant		5	NM_017950.4	ENSP00000380679	P2

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 25 AN: 19358 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00384

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000315

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 Data not reliable, filtered out with message: AS_VQSR AF: 0.000316 AC: 131 AN: 414012 Hom.: 15 Cov.: 43 AF XY: 0.000275 AC XY: 58 AN XY: 210622

Gnomad4 AFR exome AF: 0.00598

Gnomad4 AMR exome AF: 0.000176

Gnomad4 ASJ exome AF: 0.000260

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000207

Gnomad4 FIN exome AF: 0.000129

Gnomad4 NFE exome AF: 0.000115

Gnomad4 OTH exome AF: 0.000362

GnomAD4 genome AF: 0.00129 AC: 25 AN: 19358 Hom.: 1 Cov.: 0 AF XY: 0.00157 AC XY: 15 AN XY: 9546

Gnomad4 AFR AF: 0.00384

Gnomad4 AMR AF: 0.000315

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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10693712; hg19: chr17-78064145;