NM_017950.4:c.20C>A

Variant names:

• chr17-80036682-C-A
• rs750300695
• NM_017950.4:c.20C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017950.4(CCDC40):​c.20C>A​(p.Ala7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,306,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000099 (0 hom.)
• Consequence: CCDC40 NM_017950.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05585301).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.20C>A	p.Ala7Glu	missense_variant	Exon 1 of 20	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.20C>A	p.Ala7Glu	missense_variant	Exon 1 of 18		NP_001230271.1
CCDC40	NM_001330508.2	c.20C>A	p.Ala7Glu	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.20C>A	p.Ala7Glu	missense_variant	Exon 1 of 20	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000995 AC: 13 AN: 1306998 Hom.: 0 Cov.: 31 AF XY: 0.00000778 AC XY: 5 AN XY: 642314

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000335

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000115

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.033
DANN	Benign	0.82
DEOGEN2	Benign	0.020	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.45	T;T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.056	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.10	N;N;N;N
REVEL	Benign	0.018
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.87	T;T;T;T
Polyphen		0.054, 0.53	.;B;.;P
Vest4		0.10
MutPred		0.34		Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);Gain of solvent accessibility (P = 0.0261);
MVP		0.11
MPC		0.22
ClinPred		0.096	T
GERP RS		-1.3
Varity_R		0.047
gMVP		0.031

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

LitVar

Other links and lift over

dbSNP: rs750300695; hg19: chr17-78010481;