3-42735805-G-A

Variant summary

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

The NM_144719.4(CCDC13):​c.1273C>T​(p.Arg425Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCDC13
NM_144719.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.457
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18221357).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC13NM_144719.4 linkc.1273C>T p.Arg425Trp missense_variant 10/16 ENST00000310232.11 NP_653320.3 Q8IYE1Q96LI1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC13ENST00000310232.11 linkc.1273C>T p.Arg425Trp missense_variant 10/161 NM_144719.4 ENSP00000309836.6 Q8IYE1
ENSG00000280571ENST00000648550.1 linkc.1342C>T p.Arg448Trp missense_variant 11/17 ENSP00000496982.1 A0A3B3IRZ5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152194
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251408
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
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:
0.00000274
AC:
4
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000547
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1

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 GeneticsNov 17, 2023The c.1273C>T (p.R425W) alteration is located in exon 10 (coding exon 9) of the CCDC13 gene. This alteration results from a C to T substitution at nucleotide position 1273, causing the arginine (R) at amino acid position 425 to be replaced by a tryptophan (W). 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
0.11
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.028
.;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.27
FATHMM_MKL
Benign
0.41
N
LIST_S2
Benign
0.80
T;T
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-3.4
.;D
REVEL
Benign
0.059
Sift
Uncertain
0.0040
.;D
Sift4G
Uncertain
0.0040
.;D
Polyphen
0.99
.;D
Vest4
0.36
MutPred
0.32
.;Loss of disorder (P = 0.0087);
MVP
0.54
MPC
0.60
ClinPred
0.94
D
GERP RS
0.73
Varity_R
0.14
gMVP
0.20

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: rs777005407; hg19: chr3-42777297; API