Variant 19-17936443-A-G 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.23A>G(p.Glu8Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCDC124
NM_001136203.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.86

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:

CCDC124 (HGNC:):

CCDC124 links:

Genome browser will be placed here

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.23A>G	p.Glu8Gly	missense_variant	2/5	ENST00000445755.7	NP_001129675.1	Q96CT7A0A024R7M8
CCDC124	NM_138442.4 linkuse as main transcript	c.23A>G	p.Glu8Gly	missense_variant	2/5		NP_612451.1	Q96CT7A0A024R7M8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC124	ENST00000445755.7 linkuse as main transcript	c.23A>G	p.Glu8Gly	missense_variant	2/5	2	NM_001136203.2	ENSP00000408730.1	Q96CT7
CCDC124	ENST00000597436.5 linkuse as main transcript	c.23A>G	p.Glu8Gly	missense_variant	2/5	1		ENSP00000471455.1	Q96CT7
CCDC124	ENST00000596123.1 linkuse as main transcript	c.23A>G	p.Glu8Gly	missense_variant	1/3	2		ENSP00000472520.1	M0R2F5
CCDC124	ENST00000602080.1 linkuse as main transcript	n.60A>G		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000121

AC:

AN:

248704

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135032

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000872

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:

0.00000205

AC:

AN:

1460996

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726730

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000672

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:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

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:

0.0000378

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

Jul 12, 2022

The c.23A>G (p.E8G) alteration is located in exon 2 (coding exon 1) of the CCDC124 gene. This alteration results from a A to G substitution at nucleotide position 23, causing the glutamic acid (E) at amino acid position 8 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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T;.

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

.;D;D

M_CAP

Benign

0.062

MetaRNN

Uncertain

0.45

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.9

D;.;.

REVEL

Benign

0.26

Sift

Benign

0.13

T;.;.

Sift4G

Benign

0.25

T;T;T

Polyphen

0.98

D;D;.

Vest4

0.75

MutPred

0.20

Gain of catalytic residue at E8 (P = 0.0342);Gain of catalytic residue at E8 (P = 0.0342);Gain of catalytic residue at E8 (P = 0.0342);

MVP

0.56

MPC

1.1

ClinPred

0.96

GERP RS

4.5

Varity_R

0.42

gMVP

0.093

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