rs199673680
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_016169.4(SUFU):c.671G>A(p.Arg224Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,614,180 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. R224W) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.671G>A | p.Arg224Gln | missense_variant | 5/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.671G>A | p.Arg224Gln | missense_variant | 5/12 | 1 | NM_016169.4 | P1 | |
SUFU | ENST00000423559.2 | c.671G>A | p.Arg224Gln | missense_variant | 5/10 | 1 | |||
SUFU | ENST00000369899.6 | c.671G>A | p.Arg224Gln | missense_variant | 5/11 | 1 | |||
SUFU | ENST00000471000.1 | n.453G>A | non_coding_transcript_exon_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251196Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135784
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727228
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74492
ClinVar
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 224 of the SUFU protein (p.Arg224Gln). This variant is present in population databases (rs199673680, gnomAD 0.006%). 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: 453972). 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 23, 2023 | The p.R224Q variant (also known as c.671G>A), located in coding exon 5 of the SUFU gene, results from a G to A substitution at nucleotide position 671. The arginine at codon 224 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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