chr6-43040971-T-TTGCAGGCATTGCTGCAGCTGTGCCAGCC
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_014780.5(CUL7):c.3749_3750insGGCTGGCACAGCTGCAGCAATGCCTGCA(p.Val1252GlyfsTer23) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000342 in 1,461,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
CUL7
NM_014780.5 frameshift
NM_014780.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.96
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 6-43040971-T-TTGCAGGCATTGCTGCAGCTGTGCCAGCC is Pathogenic according to our data. Variant chr6-43040971-T-TTGCAGGCATTGCTGCAGCTGTGCCAGCC is described in ClinVar as [Likely_pathogenic]. Clinvar id is 800566.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL7 | NM_014780.5 | c.3749_3750insGGCTGGCACAGCTGCAGCAATGCCTGCA | p.Val1252GlyfsTer23 | frameshift_variant | 20/26 | ENST00000265348.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL7 | ENST00000265348.9 | c.3749_3750insGGCTGGCACAGCTGCAGCAATGCCTGCA | p.Val1252GlyfsTer23 | frameshift_variant | 20/26 | 1 | NM_014780.5 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461026Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726730
GnomAD4 exome
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5
AN:
1461026
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32
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0
AN XY:
726730
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
3M syndrome 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Prenatal Diagnosis Center, Guizhou Provincial People's Hospital | - | - - |
Computational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at