chr10-102504165-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_016169.4(SUFU):c.13C>T(p.Arg5Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000324 in 1,544,840 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R5R) has been classified as Likely benign.
Frequency
Consequence
NM_016169.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.13C>T | p.Arg5Trp | missense_variant | 1/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.13C>T | p.Arg5Trp | missense_variant | 1/12 | 1 | NM_016169.4 | P1 | |
SUFU | ENST00000423559.2 | c.13C>T | p.Arg5Trp | missense_variant | 1/10 | 1 | |||
SUFU | ENST00000369899.6 | c.13C>T | p.Arg5Trp | missense_variant | 1/11 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000684 AC: 1AN: 146198Hom.: 0 AF XY: 0.0000126 AC XY: 1AN XY: 79538
GnomAD4 exome AF: 0.00000215 AC: 3AN: 1392678Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1AN XY: 687018
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74316
ClinVar
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 15, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 5 of the SUFU protein (p.Arg5Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 956096). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 | May 12, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2024 | The p.R5W variant (also known as c.13C>T), located in coding exon 1 of the SUFU gene, results from a C to T substitution at nucleotide position 13. The arginine at codon 5 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at