rs200678214

Variant names:

• chr17-80047386-C-A
• NM_017950.4:c.660C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80047386-C-A
• chr17-80047386-C-G
• chr17-80047386-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017950.4(CCDC40):​c.660C>A​(p.Phe220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC40 NM_017950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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]

ENSG00000289689 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.660C>A	p.Phe220Leu	missense_variant	Exon 4 of 20	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.660C>A	p.Phe220Leu	missense_variant	Exon 4 of 18		NP_001230271.1
CCDC40	NM_001330508.2	c.660C>A	p.Phe220Leu	missense_variant	Exon 4 of 11		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.660C>A	p.Phe220Leu	missense_variant	Exon 4 of 20	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460600 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.33
DANN	Benign	0.26
DEOGEN2	Benign	0.021	.;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.48	T;T;T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.026	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.32	N;N;N;N
REVEL	Benign	0.019
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.74	T;T;T;T
Polyphen		0.0, 0.0020	.;B;.;B
Vest4		0.092
MutPred		0.16		Loss of glycosylation at S222 (P = 0.1695);Loss of glycosylation at S222 (P = 0.1695);Loss of glycosylation at S222 (P = 0.1695);Loss of glycosylation at S222 (P = 0.1695);
MVP		0.040
MPC		0.20
ClinPred		0.016	T
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.031
gMVP		0.058

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.27		Position offset: 16

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78021185;