Variant 19-17943333-G-T 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.422G>T(p.Ser141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,594,480 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 25)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CCDC124
NM_001136203.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

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=0.15369245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2 linkuse as main transcript	c.422G>T	p.Ser141Ile	missense_variant	4/5	ENST00000445755.7	NP_001129675.1	Q96CT7A0A024R7M8
CCDC124	NM_138442.4 linkuse as main transcript	c.422G>T	p.Ser141Ile	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.422G>T	p.Ser141Ile	missense_variant	4/5	2	NM_001136203.2	ENSP00000408730.1	Q96CT7
CCDC124	ENST00000597436.5 linkuse as main transcript	c.422G>T	p.Ser141Ile	missense_variant	4/5	1		ENSP00000471455.1	Q96CT7
CCDC124	ENST00000596123.1 linkuse as main transcript	c.*12G>T		downstream_gene_variant		2		ENSP00000472520.1	M0R2F5

Frequencies

GnomAD3 genomes

AF:

0.0000863

AC:

AN:

150646

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.0000139

AC:

AN:

215390

Hom.:

AF XY:

0.00

AC XY:

AN XY:

117320

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000485

AC:

AN:

1443726

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

716600

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000862

AC:

AN:

150754

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73580

show subpopulations

Gnomad4 AFR

AF:

0.000317

Gnomad4 AMR

AF:

0.00

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:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.00000836

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

Nov 17, 2023

The c.422G>T (p.S141I) alteration is located in exon 4 (coding exon 3) of the CCDC124 gene. This alteration results from a G to T substitution at nucleotide position 422, causing the serine (S) at amino acid position 141 to be replaced by an isoleucine (I). 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

0.17

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.041

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.83

.;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.014

Sift

Benign

0.20

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.027

B;B

Vest4

0.46

MutPred

0.46

Loss of disorder (P = 0.0354);Loss of disorder (P = 0.0354);

MVP

0.41

MPC

0.40

ClinPred

0.099

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.51

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