rs145193058

Variant summary

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

The NM_001012614.2(CTBP1):​c.1273G>T​(p.Ala425Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000088 in 1,136,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A425D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 8.8e-7 ( 0 hom. )

Consequence

CTBP1
NM_001012614.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.13
Variant links:
Genes affected
CTBP1 (HGNC:2494): (C-terminal binding protein 1) This gene encodes a protein that binds to the C-terminus of adenovirus E1A proteins. This phosphoprotein is a transcriptional repressor and may play a role during cellular proliferation. This protein and the product of a second closely related gene, CTBP2, can dimerize. Both proteins can also interact with a polycomb group protein complex which participates in regulation of gene expression during development. Alternative splicing of transcripts from this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]
CTBP1-AS (HGNC:48337): (CTBP1 antisense RNA)

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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=0.07636246).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CTBP1NM_001012614.2 linkc.1273G>T p.Ala425Ser missense_variant Exon 10 of 10 ENST00000382952.8 NP_001012632.1 Q13363-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CTBP1ENST00000382952.8 linkc.1273G>T p.Ala425Ser missense_variant Exon 10 of 10 1 NM_001012614.2 ENSP00000372411.3 Q13363-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
8.80e-7
AC:
1
AN:
1136922
Hom.:
0
Cov.:
32
AF XY:
0.00000180
AC XY:
1
AN XY:
556830
show subpopulations
Gnomad4 AFR exome
AF:
0.0000454
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.064
BayesDel_addAF
Benign
-0.058
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
10
DANN
Benign
0.71
DEOGEN2
Benign
0.34
.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.80
T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.076
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
0.36
N;N
REVEL
Benign
0.27
Sift
Benign
0.057
T;T
Sift4G
Benign
0.42
T;T
Polyphen
0.0010
.;B
Vest4
0.069
MutPred
0.13
.;Gain of phosphorylation at A436 (P = 0.0084);
MVP
0.59
MPC
0.42
ClinPred
0.13
T
GERP RS
-9.4
Varity_R
0.028
gMVP
0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-1206045; API