Variant rs200858130 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_017950.4(CCDC40):c.1480C>G(p.Arg494Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,944 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CCDC40
NM_017950.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

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]

CCDC40 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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/exons	MANE	Protein
CCDC40	NM_017950.4 linkuse as main transcript	c.1480C>G	p.Arg494Gly	missense_variant	10/20	ENST00000397545.9	NP_060420.2
LOC124904074	XR_007065931.1 linkuse as main transcript	n.305+5708G>C		intron_variant, non_coding_transcript_variant
CCDC40	NM_001243342.2 linkuse as main transcript	c.1480C>G	p.Arg494Gly	missense_variant	10/18		NP_001230271.1
CCDC40	NM_001330508.2 linkuse as main transcript	c.1480C>G	p.Arg494Gly	missense_variant	10/11		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.1480C>G	p.Arg494Gly	missense_variant	10/20	5	NM_017950.4	ENSP00000380679	P2	Q4G0X9-1
	ENST00000695611.1 linkuse as main transcript	n.313+5708G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

248788

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135248

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460944

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726806

show subpopulations

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.050

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.42

.;T;.

Eigen

Benign

0.12

Eigen_PC

Benign

0.042

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.057

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.4

M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.038

D;D;D

Polyphen

0.93

.;P;.

Vest4

0.56

MutPred

0.24

Loss of MoRF binding (P = 0.0281);Loss of MoRF binding (P = 0.0281);Loss of MoRF binding (P = 0.0281);

MVP

0.55

MPC

0.40

ClinPred

0.92

GERP RS

4.8

Varity_R

0.43

gMVP

0.094

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over