rs150569584
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2
The NM_016169.4(SUFU):c.528C>T(p.His176=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,614,148 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
SUFU
NM_016169.4 synonymous
NM_016169.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.50
Genes affected
SUFU (HGNC:16466): (SUFU negative regulator of hedgehog signaling) The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
Variant 10-102592655-C-T is Benign according to our data. Variant chr10-102592655-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 298572.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Benign=2, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=1.5 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00136 (207/152336) while in subpopulation AFR AF= 0.00474 (197/41572). AF 95% confidence interval is 0.0042. There are 1 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 207 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.528C>T | p.His176= | synonymous_variant | 4/12 | ENST00000369902.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.528C>T | p.His176= | synonymous_variant | 4/12 | 1 | NM_016169.4 | P1 | |
SUFU | ENST00000423559.2 | c.528C>T | p.His176= | synonymous_variant | 4/10 | 1 | |||
SUFU | ENST00000369899.6 | c.528C>T | p.His176= | synonymous_variant | 4/11 | 1 | |||
SUFU | ENST00000471000.1 | n.310C>T | non_coding_transcript_exon_variant | 2/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00136 AC: 207AN: 152218Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000338 AC: 85AN: 251408Hom.: 1 AF XY: 0.000272 AC XY: 37AN XY: 135872
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GnomAD4 exome AF: 0.000131 AC: 191AN: 1461812Hom.: 0 Cov.: 32 AF XY: 0.000117 AC XY: 85AN XY: 727200
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GnomAD4 genome ? AF: 0.00136 AC: 207AN: 152336Hom.: 1 Cov.: 32 AF XY: 0.00140 AC XY: 104AN XY: 74498
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | SUFU: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 04, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 08, 2023 | 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 29, 2020 | - - |
Medulloblastoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Gorlin syndrome;C0025149:Medulloblastoma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at