chr5-69320398-G-A

Variant summary

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

The NM_176816.5(CCDC125):​c.143C>T​(p.Ser48Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000129 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CCDC125
NM_176816.5 missense

Scores

7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38
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=0.017767817).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC125NM_176816.5 linkuse as main transcriptc.143C>T p.Ser48Phe missense_variant 2/12 ENST00000396496.7 NP_789786.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC125ENST00000396496.7 linkuse as main transcriptc.143C>T p.Ser48Phe missense_variant 2/125 NM_176816.5 ENSP00000379754 P1Q86Z20-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
151986
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00404
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000302
AC:
76
AN:
251474
Hom.:
0
AF XY:
0.000235
AC XY:
32
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00645
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000131
AC:
192
AN:
1461852
Hom.:
0
Cov.:
32
AF XY:
0.000124
AC XY:
90
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00532
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.000530
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
151986
Hom.:
0
Cov.:
31
AF XY:
0.0000943
AC XY:
7
AN XY:
74218
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00404
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000728
Hom.:
0
Bravo
AF:
0.000132
ExAC
AF:
0.000181
AC:
22
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 16, 2022The c.143C>T (p.S48F) alteration is located in exon 1 (coding exon 1) of the CCDC125 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the serine (S) at amino acid position 48 to be replaced by a phenylalanine (F). 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
0.12
BayesDel_addAF
Benign
-0.074
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.93
D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.018
T;T;T
MetaSVM
Benign
-0.41
T
MutationAssessor
Uncertain
2.5
M;M;.
MutationTaster
Benign
0.53
D;D;D;D
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-2.1
N;N;N
REVEL
Benign
0.22
Sift
Uncertain
0.023
D;D;D
Sift4G
Uncertain
0.020
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.49
MutPred
0.20
Loss of phosphorylation at S48 (P = 0.002);Loss of phosphorylation at S48 (P = 0.002);Loss of phosphorylation at S48 (P = 0.002);
MVP
0.22
MPC
0.41
ClinPred
0.13
T
GERP RS
5.0
Varity_R
0.10
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs111417600; hg19: chr5-68616225; COSMIC: COSV67288642; API