rs199503570

Variant names:

• chr3-42733569-C-A
• rs199503570
• NM_144719.4:c.1412G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-42733569-C-A
• chr3-42733569-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144719.4(CCDC13):​c.1412G>T​(p.Arg471Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R471C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC13 NM_144719.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.769
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05133176).

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.1412G>T	p.Arg471Leu	missense	Exon 11 of 16	NP_653320.3
	CCDC13-AS1	NR_046732.1		n.84+911C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC13	ENST00000310232.11	TSL:1 MANE Select	c.1412G>T	p.Arg471Leu	missense	Exon 11 of 16	ENSP00000309836.6	Q8IYE1
	ENSG00000280571	ENST00000648550.1		c.1481G>T	p.Arg494Leu	missense	Exon 12 of 17	ENSP00000496982.1	A0A3B3IRZ5
	CCDC13	ENST00000954780.1		c.1307G>T	p.Arg436Leu	missense	Exon 10 of 15	ENSP00000624839.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250630 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460974 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726726

African (AFR) AF: 0.00 AC: 0 AN: 33400

American (AMR) AF: 0.00 AC: 0 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111556

Other (OTH) AF: 0.00 AC: 0 AN: 60360

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	5.9
DANN	Benign	0.53
DEOGEN2	Benign	0.00090	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.77
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.022
Sift	Benign	0.23	T
Sift4G	Benign	0.29	T
Polyphen		0.010	B
Vest4		0.13
MutPred		0.21		Loss of phosphorylation at S474 (P = 0.0681)
MVP		0.048
MPC		0.23
ClinPred		0.033	T
GERP RS		1.8
Varity_R		0.046
gMVP		0.28
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs199503570; hg19: chr3-42775061;