Variant 3-42739639-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_144719.4(CCDC13):c.1159C>G(p.Leu387Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,613,548 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CCDC13
NM_144719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.32

Variant links:

Genes affected

CCDC13 (HGNC:26358): (coiled-coil domain containing 13) Involved in cellular response to DNA damage stimulus; cytoplasmic microtubule organization; and non-motile cilium assembly. Located in centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC13 links:

ENSG00000280571 (HGNC:):

ENSG00000280571 links:

CCDC13-AS1 (HGNC:41142): (CCDC13 antisense RNA 1)

CCDC13-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40121454).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC13	NM_144719.4 link	c.1159C>G	p.Leu387Val	missense_variant	9/16	ENST00000310232.11	NP_653320.3	Q8IYE1Q96LI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC13	ENST00000310232.11 link	c.1159C>G	p.Leu387Val	missense_variant	9/16	1	NM_144719.4	ENSP00000309836.6		Q8IYE1
ENSG00000280571	ENST00000648550.1 link	c.1228C>G	p.Leu410Val	missense_variant	10/17			ENSP00000496982.1		A0A3B3IRZ5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461342

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726980

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:

0.0000171

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 02, 2022

The c.1159C>G (p.L387V) alteration is located in exon 9 (coding exon 8) of the CCDC13 gene. This alteration results from a C to G substitution at nucleotide position 1159, causing the leucine (L) at amino acid position 387 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.40

T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Uncertain

2.5

.;M

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

.;D

REVEL

Benign

0.25

Sift

Uncertain

0.012

.;D

Sift4G

Uncertain

0.046

.;D

Polyphen

1.0

.;D

Vest4

0.76

MutPred

0.33

.;Loss of ubiquitination at K392 (P = 0.0573);

MVP

0.42

MPC

0.74

ClinPred

0.98

GERP RS

4.2

Varity_R

0.31

gMVP

0.35

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over