chr5-69313986-T-A

Variant summary

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

The NM_176816.5(CCDC125):​c.365A>T​(p.Glu122Val) variant causes a missense, splice region 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. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CCDC125
NM_176816.5 missense, splice_region

Scores

6
12
Splicing: ADA: 0.1770
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14
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=0.12531316).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCDC125NM_176816.5 linkuse as main transcriptc.365A>T p.Glu122Val missense_variant, splice_region_variant 3/12 ENST00000396496.7 NP_789786.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCDC125ENST00000396496.7 linkuse as main transcriptc.365A>T p.Glu122Val missense_variant, splice_region_variant 3/125 NM_176816.5 ENSP00000379754 P1Q86Z20-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
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 GeneticsAug 02, 2021The c.365A>T (p.E122V) alteration is located in exon 2 (coding exon 2) of the CCDC125 gene. This alteration results from a A to T substitution at nucleotide position 365, causing the glutamic acid (E) at amino acid position 122 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
Benign
0.26
BayesDel_addAF
Benign
-0.098
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.15
T;T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.45
FATHMM_MKL
Uncertain
0.76
D
M_CAP
Benign
0.027
D
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Uncertain
2.5
M;M;.
MutationTaster
Benign
0.74
D;D;D;D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-4.3
D;D;D
REVEL
Benign
0.097
Sift
Uncertain
0.0060
D;D;D
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
0.53
P;P;.
Vest4
0.45
MutPred
0.25
Gain of catalytic residue at E122 (P = 0.0042);Gain of catalytic residue at E122 (P = 0.0042);.;
MVP
0.061
MPC
0.080
ClinPred
0.78
D
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.25
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.18
dbscSNV1_RF
Benign
0.48
SpliceAI score (max)
0.43
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.43
Position offset: -1

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: chr5-68609813; API