5-180569263-T-C

Variant names:

• chr5-180569263-T-C
• NM_001370472.1:c.1181T>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370472.1(CNOT6):​c.1181T>C​(p.Leu394Pro) variant causes a missense change. 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: 33)
• Consequence: CNOT6 NM_001370472.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32663226).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370472.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT6	NM_001370472.1	MANE Select	c.1181T>C	p.Leu394Pro	missense	Exon 10 of 12	NP_001357401.1	Q9ULM6
	CNOT6	NM_001370473.1		c.1166T>C	p.Leu389Pro	missense	Exon 10 of 12	NP_001357402.1
	CNOT6	NM_001370474.1		c.896T>C	p.Leu299Pro	missense	Exon 9 of 11	NP_001357403.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT6	ENST00000261951.9	TSL:5 MANE Select	c.1181T>C	p.Leu394Pro	missense	Exon 10 of 12	ENSP00000261951.4	Q9ULM6
	CNOT6	ENST00000393356.7	TSL:1	c.1181T>C	p.Leu394Pro	missense	Exon 12 of 14	ENSP00000377024.1	Q9ULM6
	CNOT6	ENST00000618123.4	TSL:1	c.1181T>C	p.Leu394Pro	missense	Exon 11 of 13	ENSP00000481893.1	Q9ULM6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.17
Sift	Benign	0.30	T
Sift4G	Benign	0.19	T
Polyphen		0.95	P
Vest4		0.25
MutPred		0.70		Loss of stability (P = 0.0027)
MVP		0.43
MPC		1.1
ClinPred		0.50	D
GERP RS		5.9
Varity_R		0.16
gMVP		0.85
Mutation Taster		=41/59	disease causing

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

Other links and lift over

hg19: chr5-179996263;