dbSNP rs371554766: CCDC13:p.Thr519Met (chr3-42732926-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144719.4(CCDC13):c.1556C>T(p.Thr519Met) variant causes a missense change. The variant allele was found at a frequency of 0.000015 in 1,402,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CCDC13
NM_144719.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.83

Variant links:

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]

CCDC13 links:

ENSG00000280571 (HGNC:):

ENSG00000280571 links:

CCDC13-AS1 (HGNC:41142): (CCDC13 antisense RNA 1)

CCDC13-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23462543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC13	NM_144719.4 link	c.1556C>T	p.Thr519Met	missense_variant	Exon 12 of 16	ENST00000310232.11	NP_653320.3	Q8IYE1Q96LI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC13	ENST00000310232.11 link	c.1556C>T	p.Thr519Met	missense_variant	Exon 12 of 16	1	NM_144719.4	ENSP00000309836.6		Q8IYE1
ENSG00000280571	ENST00000648550.1 link	c.1625C>T	p.Thr542Met	missense_variant	Exon 13 of 17			ENSP00000496982.1		A0A3B3IRZ5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000436

AC:

AN:

160532

Hom.:

AF XY:

0.0000473

AC XY:

AN XY:

84532

show subpopulations

Gnomad AFR exome

AF:

0.000110

Gnomad AMR exome

AF:

0.000119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000871

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1402300

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

691878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000830

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000378

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000111

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000464

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 03, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1556C>T (p.T519M) alteration is located in exon 12 (coding exon 11) of the CCDC13 gene. This alteration results from a C to T substitution at nucleotide position 1556, causing the threonine (T) at amino acid position 519 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0046

.;T

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.23

Sift

Benign

0.042

.;D

Sift4G

Uncertain

0.010

.;D

Polyphen

1.0

.;D

Vest4

0.62

MVP

0.57

MPC

0.75

ClinPred

0.28

GERP RS

6.1

Varity_R

0.073

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over