rs763598499
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_016169.4(SUFU):āc.848A>Gā(p.Glu283Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,461,826 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E283A) has been classified as Uncertain significance.
Frequency
Consequence
NM_016169.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.848A>G | p.Glu283Gly | missense_variant | 7/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.848A>G | p.Glu283Gly | missense_variant | 7/12 | 1 | NM_016169.4 | P1 | |
SUFU | ENST00000423559.2 | c.848A>G | p.Glu283Gly | missense_variant | 7/10 | 1 | |||
SUFU | ENST00000369899.6 | c.848A>G | p.Glu283Gly | missense_variant | 7/11 | 1 | |||
SUFU | ENST00000471000.1 | n.630A>G | non_coding_transcript_exon_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251430Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727214
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 283 of the SUFU protein (p.Glu283Gly). This variant is present in population databases (rs763598499, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SUFU-related conditions. ClinVar contains an entry for this variant (Variation ID: 582319). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SUFU protein function. 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. - |
Familial meningioma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 05, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 17, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at