7-135362923-T-C

Variant names:

• chr7-135362923-T-C
• rs1219674854
• NM_001190850.2:c.2104A>G

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.2104A>G​(p.Thr702Ala) 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. 9/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T702P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNOT4 NM_001190850.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.10
• 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=0.21320322).

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.2104A>G	p.Thr702Ala	missense	Exon 12 of 12	NP_001177779.1	O95628-10
	CNOT4	NM_001393370.1		c.2104A>G	p.Thr702Ala	missense	Exon 13 of 13	NP_001380299.1	O95628-10
	CNOT4	NM_001190849.2		c.2095A>G	p.Thr699Ala	missense	Exon 12 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.2104A>G	p.Thr702Ala	missense	Exon 12 of 12	ENSP00000445508.1	O95628-10
	CNOT4	ENST00000423368.6	TSL:1	c.1891A>G	p.Thr631Ala	missense	Exon 11 of 11	ENSP00000406777.2	O95628-4
	CNOT4	ENST00000361528.8	TSL:1	c.1882A>G	p.Thr628Ala	missense	Exon 11 of 11	ENSP00000354673.4	O95628-8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T
Eigen	Benign	0.064
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.21	T
PhyloP100		6.1
Sift4G	Benign	0.30	T
Vest4		0.20
MVP		0.91
ClinPred		0.88	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=68/32	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

dbSNP: rs1219674854; hg19: chr7-135047675;