Variant 19-17943332-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001136203.2(CCDC124):c.421A>G(p.Ser141Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,341,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CCDC124
NM_001136203.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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 Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity CC124_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10142255).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2 linkuse as main transcript	c.421A>G	p.Ser141Gly	missense_variant	4/5	ENST00000445755.7	NP_001129675.1	Q96CT7A0A024R7M8
CCDC124	NM_138442.4 linkuse as main transcript	c.421A>G	p.Ser141Gly	missense_variant	4/5		NP_612451.1	Q96CT7A0A024R7M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC124	ENST00000445755.7 linkuse as main transcript	c.421A>G	p.Ser141Gly	missense_variant	4/5	2	NM_001136203.2	ENSP00000408730.1	Q96CT7
CCDC124	ENST00000597436.5 linkuse as main transcript	c.421A>G	p.Ser141Gly	missense_variant	4/5	1		ENSP00000471455.1	Q96CT7
CCDC124	ENST00000596123.1 linkuse as main transcript	c.*11A>G		downstream_gene_variant		2		ENSP00000472520.1	M0R2F5

Frequencies

GnomAD3 genomes

AF:

0.0000239

AC:

AN:

125530

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000302

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000101

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:

0.000566

GnomAD4 exome

AF:

0.0000222

AC:

AN:

1215606

Hom.:

Cov.:

AF XY:

0.0000216

AC XY:

AN XY:

601358

show subpopulations

Gnomad4 AFR exome

AF:

0.000264

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000556

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000313

Gnomad4 OTH exome

AF:

0.000361

GnomAD4 genome

AF:

0.0000478

AC:

AN:

125562

Hom.:

Cov.:

AF XY:

0.0000510

AC XY:

AN XY:

58862

show subpopulations

Gnomad4 AFR

AF:

0.0000302

Gnomad4 AMR

AF:

0.000101

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00225

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000227

Asia WGS

AF:

0.00693

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 08, 2024

The c.421A>G (p.S141G) alteration is located in exon 4 (coding exon 3) of the CCDC124 gene. This alteration results from a A to G substitution at nucleotide position 421, causing the serine (S) at amino acid position 141 to be replaced by a glycine (G). 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

0.069

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.4

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

0.79

N;.

REVEL

Benign

0.029

Sift

Benign

0.40

T;.

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;B

Vest4

0.38

MutPred

0.41

Loss of phosphorylation at S141 (P = 0.0471);Loss of phosphorylation at S141 (P = 0.0471);

MVP

0.32

MPC

0.30

ClinPred

0.14

GERP RS

2.6

Varity_R

0.080

gMVP

0.32

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