chr6-43216394-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015089.4(CUL9):c.6173A>C(p.His2058Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,613,862 control chromosomes in the GnomAD database, including 54,616 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 12157 hom., cov: 33)

Exomes 𝑓: 0.23 ( 42459 hom. )

Consequence

CUL9
NM_015089.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.86

Publications

41 publications found

Variant links:

Genes affected

CUL9 (HGNC:15982): (cullin 9) Predicted to enable several functions, including ATP binding activity; metal ion binding activity; and ubiquitin protein ligase binding activity. Involved in microtubule cytoskeleton organization; protein ubiquitination; and regulation of mitotic nuclear division. Located in cytosol. Part of cullin-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

CUL9 links:

ENSG00000245261 (HGNC:58240):

ENSG00000245261 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.3749712E-6).

BP6

Variant 6-43216394-A-C is Benign according to our data. Variant chr6-43216394-A-C is described in CliVar as Benign. Clinvar id is 3058940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-43216394-A-C is described in CliVar as Benign. Clinvar id is 3058940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-43216394-A-C is described in CliVar as Benign. Clinvar id is 3058940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-43216394-A-C is described in CliVar as Benign. Clinvar id is 3058940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-43216394-A-C is described in CliVar as Benign. Clinvar id is 3058940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-43216394-A-C is described in CliVar as Benign. Clinvar id is 3058940.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-43216394-A-C is described in CliVar as Benign. Clinvar id is 3058940.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL9	NM_015089.4 link	c.6173A>C	p.His2058Pro	missense_variant	Exon 31 of 41	ENST00000252050.9	NP_055904.1	Q8IWT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL9	ENST00000252050.9 link	c.6173A>C	p.His2058Pro	missense_variant	Exon 31 of 41	5	NM_015089.4	ENSP00000252050.4		Q8IWT3-1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

52039

AN:

151972

Hom.:

12119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.274

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.169

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.203

Gnomad OTH

AF:

0.283

GnomAD2 exomes

AF:

0.252

AC:

62971

AN:

249452

AF XY:

0.244

show subpopulations

Gnomad AFR exome

AF:

0.684

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.172

Gnomad EAS exome

AF:

0.405

Gnomad FIN exome

AF:

0.168

Gnomad NFE exome

AF:

0.197

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.226

AC:

330922

AN:

1461772

Hom.:

42459

Cov.:

AF XY:

0.225

AC XY:

163929

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.682

AC:

22825

AN:

33480

American (AMR)

AF:

0.221

AC:

9877

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.171

AC:

4475

AN:

26134

East Asian (EAS)

AF:

0.401

AC:

15904

AN:

39698

South Asian (SAS)

AF:

0.259

AC:

22381

AN:

86256

European-Finnish (FIN)

AF:

0.168

AC:

8952

AN:

53342

Middle Eastern (MID)

AF:

0.186

AC:

1075

AN:

5768

European-Non Finnish (NFE)

AF:

0.207

AC:

230461

AN:

1111978

Other (OTH)

AF:

0.248

AC:

14972

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

15825

31650

47476

63301

79126

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8342

16684

25026

33368

41710

<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:

0.343

AC:

52138

AN:

152090

Hom.:

12157

Cov.:

AF XY:

0.339

AC XY:

25168

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.670

AC:

27795

AN:

41478

American (AMR)

AF:

0.246

AC:

3757

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

599

AN:

3468

East Asian (EAS)

AF:

0.419

AC:

2161

AN:

5162

South Asian (SAS)

AF:

0.272

AC:

1314

AN:

4826

European-Finnish (FIN)

AF:

0.169

AC:

1791

AN:

10588

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.203

AC:

13825

AN:

67962

Other (OTH)

AF:

0.286

AC:

604

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1466

2931

4397

5862

7328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.249

Hom.:

24442

Bravo

AF:

0.366

TwinsUK

AF:

0.206

AC:

764

ALSPAC

AF:

0.197

AC:

760

ESP6500AA

AF:

0.662

AC:

2916

ESP6500EA

AF:

0.210

AC:

1803

ExAC

AF:

0.261

AC:

31631

Asia WGS

AF:

0.331

AC:

1151

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.195

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CUL9-related disorder

Benign:1

Oct 28, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.031

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.035

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.074

T;T

MetaRNN

Benign

0.0000024

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.0

N;.

PhyloP100

2.9

PrimateAI

Uncertain

0.50

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.17

Sift

Benign

1.0

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0

B;B

Vest4

0.034

MPC

0.51

ClinPred

0.0052

GERP RS

5.7

Varity_R

0.097

gMVP

0.35

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over