chr2-218592371-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_005444.3(CNOT9):​c.608A>G​(p.Tyr203Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

CNOT9
NM_005444.3 missense

Scores

9
4
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.11
Variant links:
Genes affected
CNOT9 (HGNC:10445): (CCR4-NOT transcription complex subunit 9) This gene encodes a member of the highly conserved RCD1 protein family. The encoded protein is a transcriptional cofactor and a core protein of the CCR4-NOT complex. It may be involved in signal transduction as well as retinoic acid-regulated cell differentiation and development. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CNOT9NM_005444.3 linkuse as main transcriptc.608A>G p.Tyr203Cys missense_variant 6/8 ENST00000273064.11 NP_005435.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CNOT9ENST00000273064.11 linkuse as main transcriptc.608A>G p.Tyr203Cys missense_variant 6/81 NM_005444.3 ENSP00000273064 P1Q92600-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.38
.;T;T;.;.
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;.;D;D;D
M_CAP
Benign
0.048
D
MetaRNN
Pathogenic
0.80
D;D;D;D;D
MetaSVM
Uncertain
-0.24
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.92
D
PROVEAN
Pathogenic
-6.4
.;D;D;D;D
REVEL
Uncertain
0.55
Sift
Benign
0.17
.;T;T;T;T
Sift4G
Benign
0.17
T;T;T;T;T
Polyphen
1.0
.;D;D;.;.
Vest4
0.72
MutPred
0.56
.;Gain of catalytic residue at S207 (P = 0.1408);Gain of catalytic residue at S207 (P = 0.1408);Gain of catalytic residue at S207 (P = 0.1408);.;
MVP
0.35
MPC
2.6
ClinPred
0.98
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.79
gMVP
0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1283268656; hg19: chr2-219457094; API