chr8-17245134-C-A

Variant names:

• chr8-17245134-C-A
• NM_013354.7:c.19G>T

Variant summary

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

The NM_013354.7(CNOT7):​c.19G>T​(p.Asp7Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNOT7 NM_013354.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.86
• Publications: 0 publications found

Genes affected

CNOT7 (HGNC:14101): (CCR4-NOT transcription complex subunit 7) The protein encoded by this gene binds to an anti-proliferative protein, B-cell translocation protein 1, which negatively regulates cell proliferation. Binding of the two proteins, which is driven by phosphorylation of the anti-proliferative protein, causes signaling events in cell division that lead to changes in cell proliferation associated with cell-cell contact. The encoded protein downregulates the innate immune response and therefore provides a therapeutic target for enhancing its antimicrobial activity against foreign agents. Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 1 and X. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013354.7. 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
	CNOT7	NM_013354.7	MANE Select	c.19G>T	p.Asp7Tyr	missense	Exon 2 of 7	NP_037486.2	Q9UIV1-1
	CNOT7	NM_001322093.2		c.19G>T	p.Asp7Tyr	missense	Exon 2 of 8	NP_001309022.1
	CNOT7	NM_001322090.2		c.19G>T	p.Asp7Tyr	missense	Exon 3 of 8	NP_001309019.1	Q9UIV1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT7	ENST00000361272.9	TSL:1 MANE Select	c.19G>T	p.Asp7Tyr	missense	Exon 2 of 7	ENSP00000355279.4	Q9UIV1-1
	CNOT7	ENST00000851024.1		c.19G>T	p.Asp7Tyr	missense	Exon 2 of 8	ENSP00000521093.1
	CNOT7	ENST00000851025.1		c.19G>T	p.Asp7Tyr	missense	Exon 2 of 7	ENSP00000521094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.9
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.97	D
Vest4		0.69
MutPred		0.33		Gain of sheet (P = 0.0266)
MVP		0.63
MPC		1.4
ClinPred		0.96	D
GERP RS		3.9
PromoterAI		-0.016	Neutral
Varity_R		0.60
gMVP		0.72
Mutation Taster		=28/72	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: chr8-17102643;