chr6-43184337-C-T

Variant names:

• chr6-43184337-C-T
• rs752419079
• NM_015089.4:c.27C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015089.4(CUL9):​c.27C>T​(p.Asp9Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CUL9 NM_015089.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL9	NM_015089.4	c.27C>T	p.Asp9Asp	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.27C>T	p.Asp9Asp	synonymous_variant	Exon 2 of 41	5	NM_015089.4	ENSP00000252050.4
CUL9	ENST00000372647.6	c.27C>T	p.Asp9Asp	synonymous_variant	Exon 2 of 41	1		ENSP00000361730.2
CUL9	ENST00000451399.5	n.102C>T		non_coding_transcript_exon_variant	Exon 2 of 5	2
CUL9	ENST00000515773.5	n.102C>T		non_coding_transcript_exon_variant	Exon 2 of 40	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398086 Hom.: 0 Cov.: 30 AF XY: 0.00000146 AC XY: 1 AN XY: 686916

African (AFR) AF: 0.0000313 AC: 1 AN: 31970

American (AMR) AF: 0.00 AC: 0 AN: 37796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22820

East Asian (EAS) AF: 0.00 AC: 0 AN: 38508

South Asian (SAS) AF: 0.00 AC: 0 AN: 77820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5484

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1074626

Other (OTH) AF: 0.00 AC: 0 AN: 57584

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.84
PhyloP100		1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs752419079; hg19: chr6-43152075;