rs527761651

Variant names:

• chr3-42739636-T-C
• rs527761651
• NM_144719.4:c.1162A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-42739636-T-C
• chr3-42739636-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144719.4(CCDC13):​c.1162A>G​(p.Met388Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC13 NM_144719.4 missense, splice_region
• Scores: Splicing: ADA: 0.003509
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.55
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09660065).

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.1162A>G	p.Met388Val	missense splice_region	Exon 9 of 16	NP_653320.3
	CCDC13-AS1	NR_046732.1		n.85-1339T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC13	ENST00000310232.11	TSL:1 MANE Select	c.1162A>G	p.Met388Val	missense splice_region	Exon 9 of 16	ENSP00000309836.6	Q8IYE1
	ENSG00000280571	ENST00000648550.1		c.1231A>G	p.Met411Val	missense splice_region	Exon 10 of 17	ENSP00000496982.1	A0A3B3IRZ5
	CCDC13	ENST00000954780.1		c.1057A>G	p.Met353Val	missense splice_region	Exon 8 of 15	ENSP00000624839.1

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250440 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

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: 6.84e-7 AC: 1 AN: 1461302 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726986

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111676

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152308 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74468

African (AFR) AF: 0.00 AC: 0 AN: 41576

American (AMR) AF: 0.000131 AC: 2 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

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	0.093
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.6
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.047
Sift	Benign	0.13	T
Sift4G	Benign	0.19	T
Polyphen		0.26	B
Vest4		0.25
MutPred		0.40		Loss of ubiquitination at K392 (P = 0.0699)
MVP		0.15
MPC		0.19
ClinPred		0.31	T
GERP RS		2.7
Varity_R		0.14
gMVP		0.13
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0035
dbscSNV1_RF	Benign	0.12
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

Other links and lift over

dbSNP: rs527761651; hg19: chr3-42781128;