rs973730126

Variant names:

• chr5-180569124-C-G
• NM_001370472.1:c.1042C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-180569124-C-G
• chr5-180569124-C-T

Variant summary

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

The NM_001370472.1(CNOT6):​c.1042C>G​(p.Leu348Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. L348F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CNOT6 NM_001370472.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.38

Genes affected

CNOT6 (HGNC:14099): (CCR4-NOT transcription complex subunit 6) This gene encodes the catalytic component of the CCR4-NOT core transcriptional regulation complex. The encoded protein has a 3'-5' RNase activity and prefers polyadenylated substrates. The CCR4-NOT complex plays a role in many cellular processes, including miRNA-mediated repression, mRNA degradation, and transcriptional regulation. [provided by RefSeq, Dec 2014]

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=0.15120566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT6	NM_001370472.1	c.1042C>G	p.Leu348Val	missense_variant	Exon 10 of 12	ENST00000261951.9	NP_001357401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT6	ENST00000261951.9	c.1042C>G	p.Leu348Val	missense_variant	Exon 10 of 12	5	NM_001370472.1	ENSP00000261951.4
CNOT6	ENST00000393356.7	c.1042C>G	p.Leu348Val	missense_variant	Exon 12 of 14	1		ENSP00000377024.1
CNOT6	ENST00000618123.4	c.1042C>G	p.Leu348Val	missense_variant	Exon 11 of 13	1		ENSP00000481893.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461328 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726942

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T;T;T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D;.;.
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.16	N;N;.
REVEL	Benign	0.12
Sift	Benign	0.62	T;T;.
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.21
MutPred		0.54		Gain of methylation at K345 (P = 0.0613);Gain of methylation at K345 (P = 0.0613);Gain of methylation at K345 (P = 0.0613);
MVP		0.24
MPC		0.62
ClinPred		0.92	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.064
gMVP		0.48

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: chr5-179996124;