chr3-42735759-C-G

Variant names:

• chr3-42735759-C-G
• NM_144719.4:c.1319G>C

Variant summary

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

The NM_144719.4(CCDC13):​c.1319G>C​(p.Arg440Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC13 NM_144719.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.47

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]

ENSG00000280571 (HGNC:):

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

ACMG classification

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 rank	MANE	Protein	UniProt
CCDC13	NM_144719.4	c.1319G>C	p.Arg440Pro	missense_variant	Exon 10 of 16	ENST00000310232.11	NP_653320.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC13	ENST00000310232.11	c.1319G>C	p.Arg440Pro	missense_variant	Exon 10 of 16	1	NM_144719.4	ENSP00000309836.6
ENSG00000280571	ENST00000648550.1	c.1388G>C	p.Arg463Pro	missense_variant	Exon 11 of 17			ENSP00000496982.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1319G>C (p.R440P) alteration is located in exon 10 (coding exon 9) of the CCDC13 gene. This alteration results from a G to C substitution at nucleotide position 1319, causing the arginine (R) at amino acid position 440 to be replaced by a proline (P). 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	.;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.86	D;D
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.7	.;D
REVEL	Benign	0.18
Sift	Benign	0.060	.;T
Sift4G	Uncertain	0.0040	.;D
Polyphen		1.0	.;D
Vest4		0.69
MutPred		0.28		.;Loss of MoRF binding (P = 0.0188);
MVP		0.62
MPC		0.88
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.80
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-42777251;