rs730880261
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_014780.5(CUL7):c.4451_4452delTG(p.Val1484GlyfsTer69) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
CUL7
NM_014780.5 frameshift
NM_014780.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.37
Publications
4 publications found
Genes affected
CUL7 (HGNC:21024): (cullin 7) The protein encoded by this gene is a component of an E3 ubiquitin-protein ligase complex. The encoded protein interacts with TP53, CUL9, and FBXW8 proteins. Defects in this gene are a cause of 3M syndrome type 1 (3M1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
CUL7 Gene-Disease associations (from GenCC):
- 3M syndrome 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- 3-M syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-43038680-CCA-C is Pathogenic according to our data. Variant chr6-43038680-CCA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_014780.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CUL7 | NM_014780.5 | MANE Select | c.4451_4452delTG | p.Val1484GlyfsTer69 | frameshift | Exon 24 of 26 | NP_055595.2 | ||
| CUL7 | NM_001168370.2 | c.4547_4548delTG | p.Val1516GlyfsTer69 | frameshift | Exon 24 of 26 | NP_001161842.2 | |||
| CUL7 | NM_001374872.1 | c.4547_4548delTG | p.Val1516GlyfsTer69 | frameshift | Exon 24 of 26 | NP_001361801.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CUL7 | ENST00000265348.9 | TSL:1 MANE Select | c.4451_4452delTG | p.Val1484GlyfsTer69 | frameshift | Exon 24 of 26 | ENSP00000265348.4 | ||
| CUL7 | ENST00000674100.1 | c.4547_4548delTG | p.Val1516GlyfsTer69 | frameshift | Exon 24 of 26 | ENSP00000501292.1 | |||
| CUL7 | ENST00000674134.1 | c.4547_4548delTG | p.Val1516GlyfsTer69 | frameshift | Exon 24 of 26 | ENSP00000501068.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461808Hom.: 0 AF XY: 0.00000963 AC XY: 7AN XY: 727204 show subpopulations
GnomAD4 exome
AF:
AC:
11
AN:
1461808
Hom.:
AF XY:
AC XY:
7
AN XY:
727204
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86254
European-Finnish (FIN)
AF:
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
AC:
1
AN:
5728
European-Non Finnish (NFE)
AF:
AC:
10
AN:
1111994
Other (OTH)
AF:
AC:
0
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.443
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
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>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
4
-
-
3M syndrome 1 (4)
1
-
-
CUL7-related disorder (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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