Variant 3-123931421-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001366335.1(CCDC14):c.1532T>C(p.Ile511Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000498 in 1,404,394 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: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

CCDC14
NM_001366335.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.57

Variant links:

Genes affected

CCDC14 (HGNC:25766): (coiled-coil domain containing 14) Involved in protein localization to centrosome. Located in centriolar satellite. [provided by Alliance of Genome Resources, Apr 2022]

CCDC14 links:

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ACMG classification

Classification made for transcript

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=0.37054253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC14	NM_001366335.1 linkuse as main transcript	c.1532T>C	p.Ile511Thr	missense_variant	11/13	ENST00000409697.8	NP_001353264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC14	ENST00000409697.8 linkuse as main transcript	c.1532T>C	p.Ile511Thr	missense_variant	11/13	2	NM_001366335.1	ENSP00000386866	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000113

AC:

AN:

176244

Hom.:

AF XY:

0.0000216

AC XY:

AN XY:

92592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000753

Gnomad SAS exome

AF:

0.0000426

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000498

AC:

AN:

1404394

Hom.:

Cov.:

AF XY:

0.00000432

AC XY:

AN XY:

693820

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.00000842

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.1553T>C (p.I518T) alteration is located in exon 10 (coding exon 10) of the CCDC14 gene. This alteration results from a T to C substitution at nucleotide position 1553, causing the isoleucine (I) at amino acid position 518 to be replaced by a threonine (T). 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

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

.;.;.;T;.;T;T

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

T;.;T;T;.;T;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.37

T;T;T;T;T;T;T

MetaSVM

Benign

-0.40

MutationTaster

Benign

0.93

D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.5

.;N;N;.;D;.;N

REVEL

Benign

0.19

Sift

Uncertain

0.0070

.;D;D;.;D;.;D

Sift4G

Uncertain

0.0040

D;D;D;D;D;D;D

Polyphen

0.98

D;.;.;.;D;.;.

Vest4

0.73

MVP

0.71

MPC

0.30

ClinPred

0.65

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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