chr6-43037848-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_014780.5(CUL7):c.4937A>G(p.Tyr1646Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000093 in 1,613,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Y1646H) has been classified as Uncertain significance.
Frequency
Consequence
NM_014780.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUL7 | NM_014780.5 | c.4937A>G | p.Tyr1646Cys | missense_variant | 26/26 | ENST00000265348.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUL7 | ENST00000265348.9 | c.4937A>G | p.Tyr1646Cys | missense_variant | 26/26 | 1 | NM_014780.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152006Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249308Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134826
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461240Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 726880
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152006Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74254
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 10, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CUL7-related conditions. This variant is present in population databases (rs202213462, ExAC 0.01%). This sequence change replaces tyrosine with cysteine at codon 1646 of the CUL7 protein (p.Tyr1646Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at