Variant 19-17942789-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001136203.2(CCDC124):c.293C>T(p.Ala98Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000215 in 1,392,848 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CCDC124
NM_001136203.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.07

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC124	NM_001136203.2 linkuse as main transcript	c.293C>T	p.Ala98Val	missense_variant	3/5	ENST00000445755.7	NP_001129675.1	Q96CT7A0A024R7M8
CCDC124	NM_138442.4 linkuse as main transcript	c.293C>T	p.Ala98Val	missense_variant	3/5		NP_612451.1	Q96CT7A0A024R7M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC124	ENST00000445755.7 linkuse as main transcript	c.293C>T	p.Ala98Val	missense_variant	3/5	2	NM_001136203.2	ENSP00000408730.1	Q96CT7
CCDC124	ENST00000597436.5 linkuse as main transcript	c.293C>T	p.Ala98Val	missense_variant	3/5	1		ENSP00000471455.1	Q96CT7
CCDC124	ENST00000596123.1 linkuse as main transcript	c.293C>T	p.Ala98Val	missense_variant	2/3	2		ENSP00000472520.1	M0R2F5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149806

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

79330

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000896

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1392848

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

687036

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000254

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000387

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

Aug 12, 2024

The c.293C>T (p.A98V) alteration is located in exon 3 (coding exon 2) of the CCDC124 gene. This alteration results from a C to T substitution at nucleotide position 293, causing the alanine (A) at amino acid position 98 to be replaced by a valine (V). 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

0.26

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

T;T;.

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Benign

0.076

MetaRNN

Uncertain

0.56

D;D;D

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.1

M;M;.

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-3.2

D;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0060

D;.;.

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.52

MutPred

0.44

Loss of ubiquitination at K94 (P = 0.0863);Loss of ubiquitination at K94 (P = 0.0863);Loss of ubiquitination at K94 (P = 0.0863);

MVP

0.65

MPC

1.1

ClinPred

0.96

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.42

gMVP

0.31

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