rs1060501117
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_016169.4(SUFU):c.1429G>A(p.Val477Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. V477L) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.1429G>A | p.Val477Met | missense_variant | 12/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.1429G>A | p.Val477Met | missense_variant | 12/12 | 1 | NM_016169.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152216Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251448Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461866Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727230
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74374
ClinVar
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2023 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 477 of the SUFU protein (p.Val477Met). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 406400). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | 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