rs141532626
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_016169.4(SUFU):c.225G>T(p.Arg75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,098 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R75K) has been classified as Uncertain significance.
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.225G>T | p.Arg75Ser | missense_variant | 2/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.225G>T | p.Arg75Ser | missense_variant | 2/12 | 1 | NM_016169.4 | P1 | |
SUFU | ENST00000423559.2 | c.225G>T | p.Arg75Ser | missense_variant | 2/10 | 1 | |||
SUFU | ENST00000369899.6 | c.225G>T | p.Arg75Ser | missense_variant | 2/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 249056Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134820
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461878Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1AN XY: 727238
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 26, 2023 | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 75 of the SUFU protein (p.Arg75Ser). This variant is not present in population databases (gnomAD no frequency). 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: 524664). 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 with a negative predictive value of 80%. 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 | Nov 10, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 2022 | The p.R75S variant (also known as c.225G>T), located in coding exon 2 of the SUFU gene, results from a G to T substitution at nucleotide position 225. The arginine at codon 75 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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