rs770884007

Variant names:

• chr4-77742243-C-A
• rs770884007
• NM_144571.3:c.770G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-77742243-C-A
• chr4-77742243-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144571.3(CNOT6L):​c.770G>T​(p.Arg257Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNOT6L NM_144571.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18
• Publications: 0 publications found

Genes affected

CNOT6L (HGNC:18042): (CCR4-NOT transcription complex subunit 6 like) Predicted to enable poly(A)-specific ribonuclease activity. Involved in positive regulation of cell population proliferation and positive regulation of cytoplasmic mRNA processing body assembly. Located in cytosol and nucleus. Part of CCR4-NOT complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.24661651).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144571.3. 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
	CNOT6L	NM_144571.3	MANE Select	c.770G>T	p.Arg257Leu	missense	Exon 8 of 12	NP_653172.2	Q96LI5-1
	CNOT6L	NM_001387842.1		c.953G>T	p.Arg318Leu	missense	Exon 9 of 13	NP_001374771.1
	CNOT6L	NM_001387843.1		c.953G>T	p.Arg318Leu	missense	Exon 9 of 13	NP_001374772.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNOT6L	ENST00000504123.7	TSL:2 MANE Select	c.770G>T	p.Arg257Leu	missense	Exon 8 of 12	ENSP00000424896.1	Q96LI5-1
	CNOT6L	ENST00000873612.1		c.794G>T	p.Arg265Leu	missense	Exon 8 of 12	ENSP00000543671.1
	CNOT6L	ENST00000512485.6	TSL:5	c.755G>T	p.Arg252Leu	missense	Exon 8 of 12	ENSP00000425571.2	H0Y9Z5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000404 AC: 1 AN: 247294 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460638 Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4 AN XY: 726536

African (AFR) AF: 0.00 AC: 0 AN: 33450

American (AMR) AF: 0.0000224 AC: 1 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.00 AC: 0 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111402

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

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	Benign	0.17
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.24
Eigen_PC	Benign	0.044
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	-0.067	T
MutationAssessor	Benign	-0.075	N
PhyloP100		2.2
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.37
Sift	Benign	0.39	T
Sift4G	Benign	0.72	T
Polyphen		0.0010	B
Vest4		0.57
MutPred		0.33		Gain of ubiquitination at K255 (P = 0.0582)
MVP		0.72
ClinPred		0.27	T
GERP RS		6.2
Varity_R		0.68
gMVP		0.88
Mutation Taster		=36/64	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

dbSNP: rs770884007; hg19: chr4-78663397;