Genetic Variant CUL9:p.Gly106Gly (chr6-43184628-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_015089.4(CUL9):c.318C>A(p.Gly106Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,611,800 control chromosomes in the GnomAD database, including 1,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.048 ( 293 hom., cov: 32)

Exomes 𝑓: 0.030 ( 836 hom. )

Consequence

CUL9
NM_015089.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.846

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 6-43184628-C-A is Benign according to our data. Variant chr6-43184628-C-A is described in ClinVar as [Benign]. Clinvar id is 3037257.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.846 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL9	NM_015089.4 link	c.318C>A	p.Gly106Gly	synonymous_variant	Exon 2 of 41	ENST00000252050.9	NP_055904.1	Q8IWT3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CUL9	ENST00000252050.9 link	c.318C>A	p.Gly106Gly	synonymous_variant	Exon 2 of 41	5	NM_015089.4	ENSP00000252050.4	Q8IWT3-1
CUL9	ENST00000372647.6 link	c.318C>A	p.Gly106Gly	synonymous_variant	Exon 2 of 41	1		ENSP00000361730.2	E9PEZ1
CUL9	ENST00000451399.5 link	n.393C>A		non_coding_transcript_exon_variant	Exon 2 of 5	2
CUL9	ENST00000515773.5 link	n.393C>A		non_coding_transcript_exon_variant	Exon 2 of 40	2

Frequencies

GnomAD3 genomes

AF:

0.0482

AC:

7326

AN:

152146

Hom.:

292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.00250

Gnomad SAS

AF:

0.0418

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0295

Gnomad OTH

AF:

0.0416

GnomAD3 exomes

AF:

0.0318

AC:

7980

AN:

250992

Hom.:

199

AF XY:

0.0310

AC XY:

4208

AN XY:

135618

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0291

Gnomad EAS exome

AF:

0.00130

Gnomad SAS exome

AF:

0.0365

Gnomad FIN exome

AF:

0.0213

Gnomad NFE exome

AF:

0.0300

Gnomad OTH exome

AF:

0.0337

GnomAD4 exome

AF:

0.0304

AC:

44335

AN:

1459536

Hom.:

836

Cov.:

AF XY:

0.0303

AC XY:

22008

AN XY:

725548

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.0276

Gnomad4 EAS exome

AF:

0.00724

Gnomad4 SAS exome

AF:

0.0347

Gnomad4 FIN exome

AF:

0.0230

Gnomad4 NFE exome

AF:

0.0289

Gnomad4 OTH exome

AF:

0.0349

GnomAD4 genome

AF:

0.0482

AC:

7335

AN:

152264

Hom.:

293

Cov.:

AF XY:

0.0470

AC XY:

3502

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.0276

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0416

Gnomad4 FIN

AF:

0.0221

Gnomad4 NFE

AF:

0.0295

Gnomad4 OTH

AF:

0.0412

Alfa

AF:

0.0373

Hom.:

Bravo

AF:

0.0511

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0307

EpiControl

AF:

0.0292

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CUL9-related disorder

Benign:1

Dec 20, 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

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over