10-102615329-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_016169.4(SUFU):c.1084C>T(p.Arg362Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000898 in 1,614,164 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R362H) has been classified as Likely benign.
Frequency
Consequence
NM_016169.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.1084C>T | p.Arg362Cys | missense_variant | 9/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.1084C>T | p.Arg362Cys | missense_variant | 9/12 | 1 | NM_016169.4 | P1 | |
SUFU | ENST00000423559.2 | c.1084C>T | p.Arg362Cys | missense_variant | 9/10 | 1 | |||
SUFU | ENST00000369899.6 | c.1084C>T | p.Arg362Cys | missense_variant | 9/11 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000335 AC: 51AN: 152166Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000835 AC: 21AN: 251486Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135916
GnomAD4 exome AF: 0.0000643 AC: 94AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.0000646 AC XY: 47AN XY: 727244
GnomAD4 genome ? AF: 0.000335 AC: 51AN: 152284Hom.: 0 Cov.: 31 AF XY: 0.000376 AC XY: 28AN XY: 74468
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Nov 17, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 12, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with ependymoma, leukemia, or autism spectrum disorder (Zhang et al., 2015; Darbro et al., 2016); Published functional studies demonstrate that SUFU Arg362Cys prevents binding of RUSC2 or Gli3 proteins compared to wild-type (Jin et al., 2016); This variant is associated with the following publications: (PMID: 24728327, 27974047, 26934580, 27633991, 26580448) - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | May 28, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 13, 2020 | 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. - |
Gorlin syndrome;C0025149:Medulloblastoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at