3-42732926-G-T

Variant names:

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

Variant summary

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

The NM_144719.4(CCDC13):​c.1556C>A​(p.Thr519Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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=0.31529796).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC13	NM_144719.4	c.1556C>A	p.Thr519Lys	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>A	p.Thr519Lys	missense_variant	Exon 12 of 16	1	NM_144719.4	ENSP00000309836.6
ENSG00000280571	ENST00000648550.1	c.1625C>A	p.Thr542Lys	missense_variant	Exon 13 of 17			ENSP00000496982.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1402300 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691878

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0021	.;T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	.;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	.;N
REVEL	Benign	0.23
Sift	Benign	0.12	.;T
Sift4G	Uncertain	0.023	.;D
Polyphen		1.0	.;D
Vest4		0.65
MutPred		0.15		.;Gain of ubiquitination at T519 (P = 0.0082);
MVP		0.52
MPC		0.82
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.17
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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; COSMIC: COSV59607023; COSMIC: COSV59607023;