Variant 5-180567200-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001370472.1(CNOT6):c.830G>A(p.Arg277Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CNOT6
NM_001370472.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.19

Variant links:

Genes affected

CNOT6 (HGNC:14099): (CCR4-NOT transcription complex subunit 6) This gene encodes the catalytic component of the CCR4-NOT core transcriptional regulation complex. The encoded protein has a 3'-5' RNase activity and prefers polyadenylated substrates. The CCR4-NOT complex plays a role in many cellular processes, including miRNA-mediated repression, mRNA degradation, and transcriptional regulation. [provided by RefSeq, Dec 2014]

CNOT6 links:

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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=0.21485639).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT6	NM_001370472.1 linkuse as main transcript	c.830G>A	p.Arg277Lys	missense_variant	8/12	ENST00000261951.9	NP_001357401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CNOT6	ENST00000261951.9 linkuse as main transcript	c.830G>A	p.Arg277Lys	missense_variant	8/12	5	NM_001370472.1	ENSP00000261951	P1
CNOT6	ENST00000393356.7 linkuse as main transcript	c.830G>A	p.Arg277Lys	missense_variant	10/14	1		ENSP00000377024	P1
CNOT6	ENST00000618123.4 linkuse as main transcript	c.830G>A	p.Arg277Lys	missense_variant	9/13	1		ENSP00000481893	P1
CNOT6	ENST00000504343.1 linkuse as main transcript	c.542G>A	p.Arg181Lys	missense_variant	5/6	3		ENSP00000422087

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249572

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460694

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726642

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Dec 01, 2023

The c.830G>A (p.R277K) alteration is located in exon 8 (coding exon 7) of the CNOT6 gene. This alteration results from a G to A substitution at nucleotide position 830, causing the arginine (R) at amino acid position 277 to be replaced by a lysine (K). 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

0.25

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T;T;T

Eigen

Benign

0.14

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

D;.;.;D

M_CAP

Benign

0.0072

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;N;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.1

N;N;.;N

REVEL

Benign

0.083

Sift

Benign

0.16

T;T;.;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.17

B;B;B;B

Vest4

0.38

MutPred

0.48

Gain of methylation at R277 (P = 0.0074);Gain of methylation at R277 (P = 0.0074);Gain of methylation at R277 (P = 0.0074);.;

MVP

0.33

MPC

0.63

ClinPred

0.35

GERP RS

5.1

Varity_R

0.30

gMVP

0.86

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over