chr5-69282974-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.1291G>A​(p.Ala431Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,612,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

CCDC125
NM_176816.5 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.869
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=0.12765497).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC125NM_176816.5 linkuse as main transcriptc.1291G>A p.Ala431Thr missense_variant 12/12 ENST00000396496.7 NP_789786.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC125ENST00000396496.7 linkuse as main transcriptc.1291G>A p.Ala431Thr missense_variant 12/125 NM_176816.5 ENSP00000379754 P1Q86Z20-1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000200
AC:
5
AN:
249802
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135082
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:
0.0000354
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000527
AC:
77
AN:
1460342
Hom.:
0
Cov.:
32
AF XY:
0.0000358
AC XY:
26
AN XY:
726352
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:
0.0000684
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.0000659
Hom.:
0
Bravo
AF:
0.0000453
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.00000824
AC:
1
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 GeneticsApr 12, 2024The c.1291G>A (p.A431T) alteration is located in exon 11 (coding exon 11) of the CCDC125 gene. This alteration results from a G to A substitution at nucleotide position 1291, causing the alanine (A) at amino acid position 431 to be replaced by a threonine (T). 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
-0.36
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.0040
T;T;.
Eigen
Benign
0.17
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.73
D
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.3
M;M;.
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.74
N;N;N
REVEL
Benign
0.10
Sift
Benign
0.26
T;T;T
Sift4G
Benign
0.39
T;T;T
Polyphen
0.88
P;P;.
Vest4
0.091
MutPred
0.43
Loss of stability (P = 0.0697);Loss of stability (P = 0.0697);.;
MVP
0.19
MPC
0.39
ClinPred
0.49
T
GERP RS
5.4
Varity_R
0.072
gMVP
0.038

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: rs777620370; hg19: chr5-68578801; API