Variant 3-123915143-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001366335.1(CCDC14):c.2354C>T(p.Ser785Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000485 in 1,613,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00047 ( 0 hom. )

Consequence

CCDC14
NM_001366335.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0200

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0093835).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC14	NM_001366335.1 linkuse as main transcript	c.2354C>T	p.Ser785Phe	missense_variant	13/13	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.2354C>T	p.Ser785Phe	missense_variant	13/13	2	NM_001366335.1	ENSP00000386866	P1

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000743

AC:

186

AN:

250276

Hom.:

AF XY:

0.000717

AC XY:

AN XY:

135274

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000985

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.0000981

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000939

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.000472

AC:

690

AN:

1461552

Hom.:

Cov.:

AF XY:

0.000488

AC XY:

355

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00425

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000397

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000604

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000711

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000912

Hom.:

Bravo

AF:

0.000529

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.00131

EpiControl

AF:

0.00113

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

Jan 03, 2024

The c.2375C>T (p.S792F) alteration is located in exon 12 (coding exon 12) of the CCDC14 gene. This alteration results from a C to T substitution at nucleotide position 2375, causing the serine (S) at amino acid position 792 to be replaced by a phenylalanine (F). 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

-0.45

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

.;.;.;T;.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.70

T;.;T;T;.;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.0094

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.9

.;N;N;.;N;.

REVEL

Benign

0.045

Sift

Uncertain

0.0040

.;D;D;.;D;.

Sift4G

Uncertain

0.013

D;D;D;D;D;D

Polyphen

0.025

B;.;.;.;B;.

Vest4

0.21

MVP

0.48

MPC

0.37

ClinPred

0.019

GERP RS

2.4

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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