6-43184547-G-C

Variant names:

• chr6-43184547-G-C
• rs143395829
• NM_015089.4:c.237G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6 BP7

The NM_015089.4(CUL9):​c.237G>C​(p.Leu79Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,612,966 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00098 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000090 (1 hom.)
• Consequence: CUL9 NM_015089.4 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 6-43184547-G-C is Benign according to our data. Variant chr6-43184547-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 3035026.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL9	NM_015089.4	c.237G>C	p.Leu79Leu	synonymous_variant	Exon 2 of 41	ENST00000252050.9	NP_055904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL9	ENST00000252050.9	c.237G>C	p.Leu79Leu	synonymous_variant	Exon 2 of 41	5	NM_015089.4	ENSP00000252050.4
CUL9	ENST00000372647.6	c.237G>C	p.Leu79Leu	synonymous_variant	Exon 2 of 41	1		ENSP00000361730.2
CUL9	ENST00000451399.5	n.312G>C		non_coding_transcript_exon_variant	Exon 2 of 5	2
CUL9	ENST00000515773.5	n.312G>C		non_coding_transcript_exon_variant	Exon 2 of 40	2

Frequencies

GnomAD3 genomes AF: 0.000966 AC: 147 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

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: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000259 AC: 65 AN: 251216 AF XY: 0.000184

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.000232

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: 0.000653

GnomAD4 exome AF: 0.0000904 AC: 132 AN: 1460648 Hom.: 1 Cov.: 31 AF XY: 0.0000647 AC XY: 47 AN XY: 726312

African (AFR) AF: 0.00287 AC: 96 AN: 33450

American (AMR) AF: 0.000381 AC: 17 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00 AC: 0 AN: 86174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111066

Other (OTH) AF: 0.000282 AC: 17 AN: 60328

GnomAD4 genome AF: 0.000985 AC: 150 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.00102 AC XY: 76 AN XY: 74480

African (AFR) AF: 0.00267 AC: 111 AN: 41576

American (AMR) AF: 0.00229 AC: 35 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.0000428 Hom.: 0

Bravo AF: 0.00156

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CUL9-related disorder Benign:1

Apr 11, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely 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	-0.49
CADD	Benign	6.6
DANN	Benign	0.74
PhyloP100		1.4

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

Other links and lift over

dbSNP: rs143395829; hg19: chr6-43152285;