chr6-43184323-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015089.4(CUL9):​c.13C>T​(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,520,486 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: 0.000013 ( 0 hom. )

Consequence

CUL9
NM_015089.4 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21799952).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CUL9NM_015089.4 linkc.13C>T p.Arg5Trp missense_variant Exon 2 of 41 ENST00000252050.9 NP_055904.1 Q8IWT3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CUL9ENST00000252050.9 linkc.13C>T p.Arg5Trp missense_variant Exon 2 of 41 5 NM_015089.4 ENSP00000252050.4 Q8IWT3-1
CUL9ENST00000372647.6 linkc.13C>T p.Arg5Trp missense_variant Exon 2 of 41 1 ENSP00000361730.2 E9PEZ1
CUL9ENST00000451399.5 linkn.88C>T non_coding_transcript_exon_variant Exon 2 of 5 2
CUL9ENST00000515773.5 linkn.88C>T non_coding_transcript_exon_variant Exon 2 of 40 2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151982
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000452
AC:
8
AN:
177098
Hom.:
0
AF XY:
0.0000532
AC XY:
5
AN XY:
93936
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000445
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000592
Gnomad NFE exome
AF:
0.0000733
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000132
AC:
18
AN:
1368504
Hom.:
0
Cov.:
30
AF XY:
0.0000194
AC XY:
13
AN XY:
670232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000316
Gnomad4 ASJ exome
AF:
0.0000472
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000274
Gnomad4 FIN exome
AF:
0.0000198
Gnomad4 NFE exome
AF:
0.0000104
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151982
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74198
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000578
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.13C>T (p.R5W) alteration is located in exon 2 (coding exon 1) of the CUL9 gene. This alteration results from a C to T substitution at nucleotide position 13, causing the arginine (R) at amino acid position 5 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.092
T
BayesDel_noAF
Benign
-0.23
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.45
T;T
Eigen
Benign
0.0070
Eigen_PC
Benign
-0.024
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.83
T;T
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Uncertain
2.6
M;.
PrimateAI
Benign
0.38
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.28
Sift
Uncertain
0.022
D;D
Sift4G
Uncertain
0.0090
D;D
Polyphen
1.0
D;D
Vest4
0.27
MVP
0.58
MPC
0.82
ClinPred
0.55
D
GERP RS
3.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.085
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
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.

Other links and lift over

dbSNP: rs375175228; hg19: chr6-43152061; COSMIC: COSV52730494; COSMIC: COSV52730494; API