12-70330300-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014515.7(CNOT2):​c.400A>G​(p.Met134Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,590,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000011 ( 0 hom. )

Consequence

CNOT2
NM_014515.7 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.88
Variant links:
Genes affected
CNOT2 (HGNC:7878): (CCR4-NOT transcription complex subunit 2) This gene encodes a subunit of the multi-component CCR4-NOT complex. The CCR4-NOT complex regulates mRNA synthesis and degradation and is also thought to be involved in mRNA splicing, transport and localization. The encoded protein interacts with histone deacetylases and functions as a repressor of polymerase II transcription. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24771458).
BS2
High AC in GnomAdExome4 at 16 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNOT2NM_014515.7 linkc.400A>G p.Met134Val missense_variant Exon 6 of 16 ENST00000229195.8 NP_055330.1 Q9NZN8-1A0A024RBD8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNOT2ENST00000229195.8 linkc.400A>G p.Met134Val missense_variant Exon 6 of 16 1 NM_014515.7 ENSP00000229195.3 Q9NZN8-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151952
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000123
AC:
3
AN:
244056
Hom.:
0
AF XY:
0.0000152
AC XY:
2
AN XY:
131904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000304
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000680
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000111
AC:
16
AN:
1439038
Hom.:
0
Cov.:
27
AF XY:
0.0000153
AC XY:
11
AN XY:
716824
show subpopulations
Gnomad4 AFR exome
AF:
0.0000305
Gnomad4 AMR exome
AF:
0.0000231
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000473
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000639
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151952
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74220
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.069
BayesDel_addAF
Benign
-0.083
T
BayesDel_noAF
Benign
-0.17
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.070
.;T;T;.;T;T;T;.;T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.92
D;D;.;D;D;D;.;D;D
M_CAP
Benign
0.0092
T
MetaRNN
Benign
0.25
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
.;L;L;.;.;.;L;.;.
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.71
N;N;N;N;N;N;N;N;N
REVEL
Benign
0.16
Sift
Benign
0.16
T;D;D;T;D;T;D;T;T
Sift4G
Benign
0.57
T;T;T;T;T;T;T;D;T
Polyphen
0.92
.;P;P;.;.;.;P;.;.
Vest4
0.60
MutPred
0.27
Gain of catalytic residue at P133 (P = 0.0057);Gain of catalytic residue at P133 (P = 0.0057);Gain of catalytic residue at P133 (P = 0.0057);.;.;Gain of catalytic residue at P133 (P = 0.0057);Gain of catalytic residue at P133 (P = 0.0057);.;Gain of catalytic residue at P133 (P = 0.0057);
MVP
0.55
MPC
1.0
ClinPred
0.26
T
GERP RS
5.5
Varity_R
0.41
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs763477147; hg19: chr12-70724080; API