rs766542626

Variant names:

• chr4-77774704-C-A
• NM_144571.3:c.140G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-77774704-C-A
• chr4-77774704-C-T

Variant summary

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

The NM_144571.3(CNOT6L):​c.140G>T​(p.Ser47Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,434,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S47N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CNOT6L NM_144571.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.06

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

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
CNOT6L	NM_144571.3	c.140G>T	p.Ser47Ile	missense_variant	Exon 3 of 12	ENST00000504123.7	NP_653172.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT6L	ENST00000504123.7	c.140G>T	p.Ser47Ile	missense_variant	Exon 3 of 12	2	NM_144571.3	ENSP00000424896.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1434746 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 713040

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: 9.08e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	.;T;.;.;.
Eigen	Benign	-0.076
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	.;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	1.6	.;L;.;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.9	.;D;.;.;D
REVEL	Uncertain	0.52
Sift	Benign	0.069	.;T;.;.;T
Sift4G	Uncertain	0.056	.;T;.;.;.
Polyphen		0.033	.;B;.;.;.
Vest4		0.51
MutPred		0.44		.;Loss of disorder (P = 0.0127);.;.;.;
MVP		0.50
ClinPred		0.98	D
GERP RS		4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr4-78695858;