3-42732926-G-C

Variant names:

• chr3-42732926-G-C
• rs371554766
• NM_144719.4:c.1556C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_144719.4(CCDC13):​c.1556C>G​(p.Thr519Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000713 in 1,402,300 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000071 (1 hom.)
• Consequence: CCDC13 NM_144719.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.303026).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC13	NM_144719.4	c.1556C>G	p.Thr519Arg	missense_variant	Exon 12 of 16	ENST00000310232.11	NP_653320.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC13	ENST00000310232.11	c.1556C>G	p.Thr519Arg	missense_variant	Exon 12 of 16	1	NM_144719.4	ENSP00000309836.6
ENSG00000280571	ENST00000648550.1	c.1625C>G	p.Thr542Arg	missense_variant	Exon 13 of 17			ENSP00000496982.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000125 AC: 2 AN: 160532 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 84532

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: 0.0000318

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000713 AC: 10 AN: 1402300 Hom.: 1 Cov.: 30 AF XY: 0.00000578 AC XY: 4 AN XY: 691878

Gnomad4 AFR exome AF: 0.0000314

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: 0.00000741

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	.;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.24
Sift	Benign	0.19	.;T
Sift4G	Uncertain	0.015	.;D
Polyphen		1.0	.;D
Vest4		0.60
MutPred		0.11		.;Gain of MoRF binding (P = 0.0284);
MVP		0.56
MPC		0.79
ClinPred		0.82	D
GERP RS		6.1
Varity_R		0.18
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs371554766; hg19: chr3-42774418;