Variant chr19-17943702-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001136203.2(CCDC124):c.659A>G(p.Asn220Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000198 in 1,612,648 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

CCDC124
NM_001136203.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.28

Variant links:

Genes affected

CCDC124 (HGNC:25171): (coiled-coil domain containing 124) Enables RNA binding activity. Predicted to be involved in cell division. Located in cytosol and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC124 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.15530428).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2 linkuse as main transcript	c.659A>G	p.Asn220Ser	missense_variant	5/5	ENST00000445755.7	NP_001129675.1	Q96CT7A0A024R7M8
CCDC124	NM_138442.4 linkuse as main transcript	c.659A>G	p.Asn220Ser	missense_variant	5/5		NP_612451.1	Q96CT7A0A024R7M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC124	ENST00000445755.7 linkuse as main transcript	c.659A>G	p.Asn220Ser	missense_variant	5/5	2	NM_001136203.2	ENSP00000408730.1		Q96CT7
CCDC124	ENST00000597436.5 linkuse as main transcript	c.659A>G	p.Asn220Ser	missense_variant	5/5	1		ENSP00000471455.1		Q96CT7

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000214

AC:

AN:

247926

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

135026

show subpopulations

Gnomad AFR exome

AF:

0.000317

Gnomad AMR exome

AF:

0.000291

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000197

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000179

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000194

AC:

283

AN:

1460378

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

164

AN XY:

726476

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00146

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000139

Gnomad4 OTH exome

AF:

0.000364

GnomAD4 genome

AF:

0.000236

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000295

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000393

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000178

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

Oct 18, 2021

The c.659A>G (p.N220S) alteration is located in exon 5 (coding exon 4) of the CCDC124 gene. This alteration results from a A to G substitution at nucleotide position 659, causing the asparagine (N) at amino acid position 220 to be replaced by a serine (S). 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

0.078

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.065

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.2

D;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;.

Sift4G

Benign

0.11

T;T

Polyphen

0.99

D;D

Vest4

0.61

MVP

0.61

MPC

0.78

ClinPred

0.20

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.54

gMVP

0.55

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