chr5-69311145-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_176816.5(CCDC125):ā€‹c.426G>Cā€‹(p.Glu142Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,610,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.00029 ( 0 hom. )

Consequence

CCDC125
NM_176816.5 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.437
Variant links:
Genes affected
CCDC125 (HGNC:28924): (coiled-coil domain containing 125) Enables identical protein binding activity. Involved in activation of GTPase activity; negative regulation of Rho protein signal transduction; and negative regulation of cell motility. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06537941).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC125NM_176816.5 linkuse as main transcriptc.426G>C p.Glu142Asp missense_variant 4/12 ENST00000396496.7 NP_789786.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC125ENST00000396496.7 linkuse as main transcriptc.426G>C p.Glu142Asp missense_variant 4/125 NM_176816.5 ENSP00000379754 P1Q86Z20-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000599
AC:
15
AN:
250270
Hom.:
0
AF XY:
0.0000518
AC XY:
7
AN XY:
135264
show subpopulations
Gnomad AFR exome
AF:
0.0000616
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:
0.000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000287
AC:
418
AN:
1458612
Hom.:
0
Cov.:
27
AF XY:
0.000247
AC XY:
179
AN XY:
725752
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000373
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000965
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:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000893
Hom.:
0
Bravo
AF:
0.0000831
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsFeb 22, 2023The c.426G>C (p.E142D) alteration is located in exon 3 (coding exon 3) of the CCDC125 gene. This alteration results from a G to C substitution at nucleotide position 426, causing the glutamic acid (E) at amino acid position 142 to be replaced by an aspartic acid (D). 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
0.32
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
8.2
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0029
T;T;T;.
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.55
D
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.065
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M;M;.;.
MutationTaster
Benign
0.98
N;N;N;N
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.057
Sift
Benign
0.42
T;T;T;T
Sift4G
Benign
0.44
T;T;T;T
Polyphen
0.24
B;B;.;B
Vest4
0.22
MutPred
0.20
Loss of ubiquitination at K141 (P = 0.1041);Loss of ubiquitination at K141 (P = 0.1041);.;.;
MVP
0.030
MPC
0.091
ClinPred
0.090
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.088
gMVP
0.073

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.

Other links and lift over

dbSNP: rs139810828; hg19: chr5-68606972; API