NM_001190850.2:c.1414T>A

Variant names:

• chr7-135394131-A-T
• NM_001190850.2:c.1414T>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190850.2(CNOT4):​c.1414T>A​(p.Leu472Met) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNOT4 NM_001190850.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07
• Publications: 0 publications found

Genes affected

CNOT4 (HGNC:7880): (CCR4-NOT transcription complex subunit 4) The protein encoded by this gene is a subunit of the CCR4-NOT complex, a global transcriptional regulator. The encoded protein interacts with CNOT1 and has E3 ubiquitin ligase activity. Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1526798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001190850.2. 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
	CNOT4	NM_001190850.2	MANE Select	c.1414T>A	p.Leu472Met	missense	Exon 10 of 12	NP_001177779.1	O95628-10
	CNOT4	NM_001393370.1		c.1414T>A	p.Leu472Met	missense	Exon 11 of 13	NP_001380299.1	O95628-10
	CNOT4	NM_001190849.2		c.1405T>A	p.Leu469Met	missense	Exon 10 of 12	NP_001177778.1	O95628-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT4	ENST00000541284.6	TSL:5 MANE Select	c.1414T>A	p.Leu472Met	missense	Exon 10 of 12	ENSP00000445508.1	O95628-10
	CNOT4	ENST00000423368.6	TSL:1	c.1414T>A	p.Leu472Met	missense	Exon 10 of 11	ENSP00000406777.2	O95628-4
	CNOT4	ENST00000361528.8	TSL:1	c.1405T>A	p.Leu469Met	missense	Exon 10 of 11	ENSP00000354673.4	O95628-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.082
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	21
DANN	Uncertain	0.97
DEOGEN2	Benign	0.027	T
Eigen	Benign	0.013
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.23	N
REVEL	Benign	0.044
Sift	Benign	0.051	T
Sift4G	Benign	0.27	T
Polyphen		0.0050	B
Vest4		0.31
MutPred		0.23		Gain of disorder (P = 0.0615)
MVP		0.59
MPC		0.58
ClinPred		0.31	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.31
Mutation Taster		=74/26	polymorphism

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: chr7-135078883;