rs773805575
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_016169.4(SUFU):c.1329G>A(p.Met443Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_016169.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.1329G>A | p.Met443Ile | missense_variant | 11/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.1329G>A | p.Met443Ile | missense_variant | 11/12 | 1 | NM_016169.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251490Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135918
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152256Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74392
ClinVar
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2021 | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 tolerated, but these predictions have not been confirmed by published functional studies. This variant is present in population databases (rs773805575, ExAC 0.001%) but has not been reported in the literature in individuals with a SUFU-related disease. This sequence change replaces methionine with isoleucine at codon 443 of the SUFU protein (p.Met443Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2022 | The p.M443I variant (also known as c.1329G>A), located in coding exon 11 of the SUFU gene, results from a G to A substitution at nucleotide position 1329. The methionine at codon 443 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at