NM_001190850.2:c.1408T>C

Variant names:

• chr7-135394137-A-G
• NM_001190850.2:c.1408T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001190850.2(CNOT4):​c.1408T>C​(p.Ser470Pro) 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: 32)
• Consequence: CNOT4 NM_001190850.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.06

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

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=0.12525761).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT4	NM_001190850.2	c.1408T>C	p.Ser470Pro	missense_variant	Exon 10 of 12	ENST00000541284.6	NP_001177779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT4	ENST00000541284.6	c.1408T>C	p.Ser470Pro	missense_variant	Exon 10 of 12	5	NM_001190850.2	ENSP00000445508.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1408T>C (p.S470P) alteration is located in exon 10 (coding exon 9) of the CNOT4 gene. This alteration results from a T to C substitution at nucleotide position 1408, causing the serine (S) at amino acid position 470 to be replaced by a proline (P). 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	0.067
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.024	.;.;.;.;.;T
Eigen	Benign	0.077
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.82	T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.13	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.55	.;N;N;.;.;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.69	N;N;N;N;N;N
REVEL	Benign	0.070
Sift	Benign	0.17	T;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T
Polyphen		0.0, 0.96, 0.94	.;.;B;B;D;P
Vest4		0.13
MutPred		0.30		.;Gain of loop (P = 0.0097);Gain of loop (P = 0.0097);.;.;Gain of loop (P = 0.0097);
MVP		0.64
MPC		0.61
ClinPred		0.58	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.099
gMVP		0.21

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: chr7-135078889;