6-43037692-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_014780.5(CUL7):c.5093G>A(p.Arg1698Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000747 in 1,553,764 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1698L) has been classified as Uncertain significance.
Frequency
Consequence
NM_014780.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL7 | NM_014780.5 | c.5093G>A | p.Arg1698Gln | missense_variant | 26/26 | ENST00000265348.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL7 | ENST00000265348.9 | c.5093G>A | p.Arg1698Gln | missense_variant | 26/26 | 1 | NM_014780.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000169 AC: 27AN: 160096Hom.: 0 AF XY: 0.000178 AC XY: 15AN XY: 84324
GnomAD4 exome AF: 0.0000728 AC: 102AN: 1401516Hom.: 0 Cov.: 31 AF XY: 0.0000694 AC XY: 48AN XY: 691476
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74434
ClinVar
Submissions by phenotype
3M syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 10, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1698 of the CUL7 protein (p.Arg1698Gln). This variant is present in population databases (rs541161018, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with CUL7-related conditions. ClinVar contains an entry for this variant (Variation ID: 909227). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at