12-70330300-A-G
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014515.7(CNOT2):āc.400A>Gā(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
NM_014515.7 missense
Scores
1
5
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.88
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]
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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 |
---|---|---|---|---|---|---|---|---|
CNOT2 | NM_014515.7 | c.400A>G | p.Met134Val | missense_variant | Exon 6 of 16 | ENST00000229195.8 | NP_055330.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151952Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000123 AC: 3AN: 244056Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131904
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GnomAD4 exome AF: 0.0000111 AC: 16AN: 1439038Hom.: 0 Cov.: 27 AF XY: 0.0000153 AC XY: 11AN XY: 716824
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;.;T;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;.;.;.;L;.;.
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;D;D;T;D;T;D;T;T
Sift4G
Benign
T;T;T;T;T;T;T;D;T
Polyphen
0.92
.;P;P;.;.;.;P;.;.
Vest4
0.60
MutPred
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
MPC
1.0
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at