NM_017950.4:c.23C>A

Variant names:

• chr17-80036685-C-A
• NM_017950.4:c.23C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017950.4(CCDC40):​c.23C>A​(p.Ala8Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000765 in 1,307,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A8P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: CCDC40 NM_017950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0240

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082521915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.23C>A	p.Ala8Glu	missense_variant	Exon 1 of 20	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.23C>A	p.Ala8Glu	missense_variant	Exon 1 of 18		NP_001230271.1
CCDC40	NM_001330508.2	c.23C>A	p.Ala8Glu	missense_variant	Exon 1 of 11		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.23C>A	p.Ala8Glu	missense_variant	Exon 1 of 20	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.65e-7 AC: 1 AN: 1307564 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 642558

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: 9.62e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.9
DANN	Benign	0.67
DEOGEN2	Benign	0.027	.;T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.72	N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.22	T;T;T;T
Sift4G	Benign	0.37	T;D;T;T
Polyphen		0.0070, 0.67	.;B;.;P
Vest4		0.21
MutPred		0.20		Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);Gain of solvent accessibility (P = 0.0068);
MVP		0.18
MPC		0.22
ClinPred		0.11	T
GERP RS		0.56
Varity_R		0.10
gMVP		0.044

Splicing

Name	Calibrated prediction	Score	Prediction
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78010484;