Genetic Variant NM_144571.3:c.140G>A (chr4-77774704-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_144571.3(CNOT6L):c.140G>A(p.Ser47Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000252 in 1,586,810 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CNOT6L
NM_144571.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.06

Publications

0 publications found

Variant links:

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]

CNOT6L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.21583274).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNOT6L	NM_144571.3	MANE Select	c.140G>A	p.Ser47Asn	missense	Exon 3 of 12	NP_653172.2	Q96LI5-1
CNOT6L	NM_001387842.1		c.323G>A	p.Ser108Asn	missense	Exon 4 of 13	NP_001374771.1
CNOT6L	NM_001387843.1		c.323G>A	p.Ser108Asn	missense	Exon 4 of 13	NP_001374772.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNOT6L	ENST00000504123.7	TSL:2 MANE Select	c.140G>A	p.Ser47Asn	missense	Exon 3 of 12	ENSP00000424896.1	Q96LI5-1
CNOT6L	ENST00000873612.1		c.140G>A	p.Ser47Asn	missense	Exon 3 of 12	ENSP00000543671.1
CNOT6L	ENST00000512485.6	TSL:5	c.125G>A	p.Ser42Asn	missense	Exon 3 of 12	ENSP00000425571.2	H0Y9Z5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000135

AC:

AN:

221722

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000107

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:

0.00

GnomAD4 exome

AF:

0.00000209

AC:

AN:

1434748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713040

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31782

American (AMR)

AF:

0.0000776

AC:

AN:

38644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24898

East Asian (EAS)

AF:

0.00

AC:

AN:

38762

South Asian (SAS)

AF:

0.00

AC:

AN:

81860

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101190

Other (OTH)

AF:

0.00

AC:

AN:

59184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41396

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.022

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

M_CAP

Benign

0.021

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.40

PhyloP100

4.1

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

1.9

REVEL

Uncertain

0.33

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.23

MutPred

0.30

Loss of phosphorylation at S47 (P = 0.0362)

MVP

0.26

ClinPred

0.73

GERP RS

4.2

Varity_R

0.22

gMVP

0.39

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over