3-42739639-G-C

Variant summary

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

The NM_144719.4(CCDC13):ā€‹c.1159C>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000013 ( 0 hom. )

Consequence

CCDC13
NM_144719.4 missense

Scores

12
7

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

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
CCDC13NM_144719.4 linkc.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
CCDC13ENST00000310232.11 linkc.1159C>G p.Leu387Val missense_variant 9/161 NM_144719.4 ENSP00000309836.6 Q8IYE1
ENSG00000280571ENST00000648550.1 linkc.1228C>G p.Leu410Val missense_variant 10/17 ENSP00000496982.1 A0A3B3IRZ5

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152206
Hom.:
0
Cov.:
33
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:
19
AN:
1461342
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
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:
2
AN:
152206
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
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 submitterclinical testingAmbry GeneticsDec 02, 2022The 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
D
BayesDel_noAF
Uncertain
-0.080
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.35
.;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.40
T;T
MetaSVM
Uncertain
-0.21
T
MutationAssessor
Uncertain
2.5
.;M
PrimateAI
Uncertain
0.59
T
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
D
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.

Other links and lift over

dbSNP: rs1326648307; hg19: chr3-42781131; API