CNOT4 p.Val548Leu

Variant names:

• chr7-135364052-C-A
• NM_001190850.2:c.1642G>T
• CNOT4 p.Val548Leu

Your query was ambiguous. Multiple possible variants found:

• chr7-135364052-C-A
• chr7-135364052-C-G
• chr7-135364050-TAC-CAA
• chr7-135364050-TAC-AAG
• chr7-135364050-TAC-GAG
• chr7-135364050-TAC-CAG

Variant summary

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

The NM_001190850.2(CNOT4):​c.1642G>T​(p.Val548Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CNOT4 NM_001190850.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2982887).

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.1642G>T	p.Val548Leu	missense	Exon 11 of 12	NP_001177779.1	O95628-10
	CNOT4	NM_001393370.1		c.1642G>T	p.Val548Leu	missense	Exon 12 of 13	NP_001380299.1	O95628-10
	CNOT4	NM_001190849.2		c.1633G>T	p.Val545Leu	missense	Exon 11 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.1642G>T	p.Val548Leu	missense	Exon 11 of 12	ENSP00000445508.1	O95628-10
	CNOT4	ENST00000423368.6	TSL:1	c.1628-866G>T		intron	N/A	ENSP00000406777.2	O95628-4
	CNOT4	ENST00000361528.8	TSL:1	c.1619-866G>T		intron	N/A	ENSP00000354673.4	O95628-8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.87
Eigen	Benign	-0.21
Eigen_PC	Benign	0.0036
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.4
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.057
Sift	Benign	0.28	T
Sift4G	Benign	0.60	T
gMVP		0.37
Mutation Taster		=84/16	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-135048804;