chr5-69294896-G-A

Variant summary

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

The NM_176816.5(CCDC125):​c.821C>T​(p.Ala274Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000236 in 1,611,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CCDC125
NM_176816.5 missense

Scores

8
10

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 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
CCDC125NM_176816.5 linkuse as main transcriptc.821C>T p.Ala274Val missense_variant 9/12 ENST00000396496.7 NP_789786.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC125ENST00000396496.7 linkuse as main transcriptc.821C>T p.Ala274Val missense_variant 9/125 NM_176816.5 ENSP00000379754 P1Q86Z20-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.0000201
AC:
5
AN:
249226
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
134714
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000332
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000247
AC:
36
AN:
1459790
Hom.:
0
Cov.:
30
AF XY:
0.0000275
AC XY:
20
AN XY:
726236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000466
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152124
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
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
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000545
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 10, 2022The c.821C>T (p.A274V) alteration is located in exon 8 (coding exon 8) of the CCDC125 gene. This alteration results from a C to T substitution at nucleotide position 821, causing the alanine (A) at amino acid position 274 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
Uncertain
0.39
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.14
T;T;.
Eigen
Benign
0.019
Eigen_PC
Benign
-0.040
FATHMM_MKL
Uncertain
0.79
D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.50
T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Uncertain
2.6
M;M;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.51
T
PROVEAN
Uncertain
-3.1
D;D;D
REVEL
Benign
0.16
Sift
Benign
0.085
T;T;T
Sift4G
Uncertain
0.010
D;D;D
Polyphen
0.90
P;P;P
Vest4
0.81
MutPred
0.30
Loss of disorder (P = 0.0659);Loss of disorder (P = 0.0659);.;
MVP
0.27
MPC
0.067
ClinPred
0.52
D
GERP RS
3.3
Varity_R
0.071
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.14
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: rs745493733; hg19: chr5-68590723; COSMIC: COSV67287659; API