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rs387907092

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017950.4(CCDC40):c.1951C>A(p.Gln651Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,876 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. Synonymous variant affecting the same amino acid position (i.e. Q651Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 25)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CCDC40
NM_017950.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.18
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.096758425).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CCDC40NM_017950.4 linkuse as main transcriptc.1951C>A p.Gln651Lys missense_variant 12/20 ENST00000397545.9
CCDC40NM_001243342.2 linkuse as main transcriptc.1951C>A p.Gln651Lys missense_variant 12/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CCDC40ENST00000397545.9 linkuse as main transcriptc.1951C>A p.Gln651Lys missense_variant 12/205 NM_017950.4 P2Q4G0X9-1
CCDC40ENST00000574799.5 linkuse as main transcriptn.1488C>A non_coding_transcript_exon_variant 8/161
CCDC40ENST00000374877.7 linkuse as main transcriptc.1951C>A p.Gln651Lys missense_variant 12/185 A2Q4G0X9-2
CCDC40ENST00000572253.5 linkuse as main transcriptn.578C>A non_coding_transcript_exon_variant 1/62

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD3 exomes
AF:
0.00000402
AC:
1
AN:
249060
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135216
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461876
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.60
Cadd
Benign
14
Dann
Benign
0.80
Eigen
Benign
-0.52
Eigen_PC
Benign
-0.39
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.097
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.83
L;L
MutationTaster
Benign
0.89
D;D
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.38
N;N
REVEL
Benign
0.030
Sift
Benign
0.53
T;T
Sift4G
Benign
0.32
T;T
Polyphen
0.037
.;B
Vest4
0.23
MutPred
0.25
Loss of ubiquitination at K647 (P = 0.0642);Loss of ubiquitination at K647 (P = 0.0642);
MVP
0.10
MPC
0.23
ClinPred
0.044
T
GERP RS
2.8
Varity_R
0.087
gMVP
0.25

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs387907092; hg19: chr17-78055819; API