chr6-43041036-G-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_014780.5(CUL7):c.3685C>T(p.Gln1229Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
CUL7
NM_014780.5 stop_gained
NM_014780.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.72
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 6-43041036-G-A is Pathogenic according to our data. Variant chr6-43041036-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 599184.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL7 | NM_014780.5 | c.3685C>T | p.Gln1229Ter | stop_gained | 20/26 | ENST00000265348.9 | |
LOC124901318 | XR_007059581.1 | n.1G>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL7 | ENST00000265348.9 | c.3685C>T | p.Gln1229Ter | stop_gained | 20/26 | 1 | NM_014780.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 33
GnomAD4 exome
Cov.:
33
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
3M syndrome 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Hacettepe Genetic Diseases Diagnosis Center, Hacettepe University Faculty of Medicine | Oct 10, 2014 | The p.Gln1229Ter variant in CUL7 has been observed in a 6 year-old-Turkish male 3-M syndrome patient. There was parental consanguinity and autosomal recessive inheritance pattern matching for this variant. In summary, the p.Gln1229Ter variant meets our criteria to be classified as likely pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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