chr5-69306867-A-T

Variant summary

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

The NM_176816.5(CCDC125):​c.567T>A​(p.Asp189Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CCDC125
NM_176816.5 missense

Scores

8
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.81
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]

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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=0.2616244).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC125NM_176816.5 linkuse as main transcriptc.567T>A p.Asp189Glu missense_variant 6/12 ENST00000396496.7 NP_789786.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC125ENST00000396496.7 linkuse as main transcriptc.567T>A p.Asp189Glu missense_variant 6/125 NM_176816.5 ENSP00000379754 P1Q86Z20-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

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 GeneticsMay 05, 2023The c.567T>A (p.D189E) alteration is located in exon 5 (coding exon 5) of the CCDC125 gene. This alteration results from a T to A substitution at nucleotide position 567, causing the aspartic acid (D) at amino acid position 189 to be replaced by a glutamic acid (E). 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
0.51
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T;T;.
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.20
FATHMM_MKL
Benign
0.72
D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.26
T;T;T;T
MetaSVM
Benign
-0.46
T
MutationAssessor
Uncertain
2.6
M;M;.;.
MutationTaster
Benign
0.72
D;N;N;N
PrimateAI
Uncertain
0.62
T
PROVEAN
Uncertain
-2.5
N;N;N;N
REVEL
Benign
0.24
Sift
Uncertain
0.029
D;D;D;D
Sift4G
Uncertain
0.013
D;D;D;D
Polyphen
1.0
D;D;.;D
Vest4
0.52
MutPred
0.32
Gain of disorder (P = 0.1272);Gain of disorder (P = 0.1272);.;.;
MVP
0.095
MPC
0.38
ClinPred
0.96
D
GERP RS
4.6
Varity_R
0.23
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-68602694; API