5-69307992-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_176816.5(CCDC125):​c.490G>A​(p.Val164Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CCDC125
NM_176816.5 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.279
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10828084).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC125NM_176816.5 linkuse as main transcriptc.490G>A p.Val164Met missense_variant 5/12 ENST00000396496.7 NP_789786.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC125ENST00000396496.7 linkuse as main transcriptc.490G>A p.Val164Met missense_variant 5/125 NM_176816.5 ENSP00000379754 P1Q86Z20-1

Frequencies

GnomAD3 genomes
AF:
0.000151
AC:
23
AN:
152208
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000309
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000994
AC:
25
AN:
251404
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.0000615
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:
0.000202
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000194
AC:
284
AN:
1461728
Hom.:
0
Cov.:
29
AF XY:
0.000194
AC XY:
141
AN XY:
727192
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.000248
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000151
AC:
23
AN:
152208
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000309
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000261
Hom.:
0
Bravo
AF:
0.000166
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.000327
EpiControl
AF:
0.000119

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 GeneticsAug 30, 2022The c.490G>A (p.V164M) alteration is located in exon 4 (coding exon 4) of the CCDC125 gene. This alteration results from a G to A substitution at nucleotide position 490, causing the valine (V) at amino acid position 164 to be replaced by a methionine (M). 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
0.10
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
11
DANN
Benign
0.95
DEOGEN2
Benign
0.0014
T;T;T;.
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.26
N
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.61
N;N;.;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.30
N;N;N;N
REVEL
Benign
0.018
Sift
Benign
0.34
T;T;T;T
Sift4G
Benign
1.0
T;T;T;T
Polyphen
0.38
B;B;.;B
Vest4
0.21
MVP
0.11
MPC
0.076
ClinPred
0.039
T
GERP RS
2.4
Varity_R
0.029
gMVP
0.060

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs148239448; hg19: chr5-68603819; API