5-180529341-A-G

Position:

• chr5-180529341-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370472.1(CNOT6):​c.65A>G​(p.Glu22Gly) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNOT6 NM_001370472.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.39

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42104402).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNOT6	NM_001370472.1	c.65A>G	p.Glu22Gly	missense_variant	2/12	ENST00000261951.9	NP_001357401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNOT6	ENST00000261951.9	c.65A>G	p.Glu22Gly	missense_variant	2/12	5	NM_001370472.1	ENSP00000261951.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

The c.65A>G (p.E22G) alteration is located in exon 2 (coding exon 1) of the CNOT6 gene. This alteration results from a A to G substitution at nucleotide position 65, causing the glutamic acid (E) at amino acid position 22 to be replaced by a glycine (G). 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	Pathogenic	0.82
BayesDel_addAF	Benign	0.0070	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T;T;T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;.;.;D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.42	T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M;M;M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	D;D;.;N
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D;D;.;T
Sift4G	Benign	0.078	T;T;T;D
Polyphen		0.99	D;D;D;.
Vest4		0.48
MutPred		0.30		Gain of MoRF binding (P = 0.0353);Gain of MoRF binding (P = 0.0353);Gain of MoRF binding (P = 0.0353);Gain of MoRF binding (P = 0.0353);
MVP		0.72
MPC		1.4
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.36
gMVP		0.50

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: chr5-179956341;