NM_013354.7:c.19G>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT7	NM_013354.7	c.19G>T	p.Asp7Tyr	missense_variant	Exon 2 of 7	ENST00000361272.9	NP_037486.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT7	ENST00000361272.9	c.19G>T	p.Asp7Tyr	missense_variant	Exon 2 of 7	1	NM_013354.7	ENSP00000355279.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 14, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.19G>T (p.D7Y) alteration is located in exon 2 (coding exon 1) of the CNOT7 gene. This alteration results from a G to T substitution at nucleotide position 19, causing the aspartic acid (D) at amino acid position 7 to be replaced by a tyrosine (Y). 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	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;.;T;.;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.60	D;D;D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.4	M;M;.;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.4	N;D;N;D;.
REVEL	Benign	0.22
Sift	Uncertain	0.0010	D;D;D;D;.
Sift4G	Uncertain	0.0050	D;D;.;.;D
Polyphen		0.97	D;.;.;.;.
Vest4		0.69
MutPred		0.33		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.63
MPC		1.4
ClinPred		0.96	D
GERP RS		3.9
Varity_R		0.60
gMVP		0.72

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: chr8-17102643;