3-42732921-G-T

Variant names:

• chr3-42732921-G-T
• rs1157132821
• NM_144719.4:c.1561C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144719.4(CCDC13):​c.1561C>A​(p.Pro521Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000713 in 1,402,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P521S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CCDC13 NM_144719.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144719.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC13	NM_144719.4	MANE Select	c.1561C>A	p.Pro521Thr	missense	Exon 12 of 16	NP_653320.3
	CCDC13-AS1	NR_046732.1		n.84+263G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC13	ENST00000310232.11	TSL:1 MANE Select	c.1561C>A	p.Pro521Thr	missense	Exon 12 of 16	ENSP00000309836.6	Q8IYE1
	ENSG00000280571	ENST00000648550.1		c.1630C>A	p.Pro544Thr	missense	Exon 13 of 17	ENSP00000496982.1	A0A3B3IRZ5
	CCDC13	ENST00000954780.1		c.1456C>A	p.Pro486Thr	missense	Exon 11 of 15	ENSP00000624839.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000624 AC: 1 AN: 160318 AF XY: 0.0000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000397

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 7.13e-7 AC: 1 AN: 1402176 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 691828

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31802

American (AMR) AF: 0.0000277 AC: 1 AN: 36124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25188

East Asian (EAS) AF: 0.00 AC: 0 AN: 36054

South Asian (SAS) AF: 0.00 AC: 0 AN: 79388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080256

Other (OTH) AF: 0.00 AC: 0 AN: 58114

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.056	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.8
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.23
Sift	Benign	0.069	T
Sift4G	Uncertain	0.051	T
Polyphen		1.0	D
Vest4		0.54
MutPred		0.18		Gain of phosphorylation at P521 (P = 0.0789)
MVP		0.56
MPC		0.78
ClinPred		0.86	D
GERP RS		6.1
Varity_R		0.15
gMVP		0.40
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 49

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1157132821; hg19: chr3-42774413;