rs751057597
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The ENST00000369902.8(SUFU):c.849G>A(p.Glu283=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,613,906 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
SUFU
ENST00000369902.8 synonymous
ENST00000369902.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.33
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 10-102597232-G-A is Benign according to our data. Variant chr10-102597232-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 524667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.33 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00000889 (13/1461830) while in subpopulation SAS AF= 0.0000927 (8/86258). AF 95% confidence interval is 0.0000458. There are 0 homozygotes in gnomad4_exome. There are 11 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SUFU | NM_016169.4 | c.849G>A | p.Glu283= | synonymous_variant | 7/12 | ENST00000369902.8 | NP_057253.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SUFU | ENST00000369902.8 | c.849G>A | p.Glu283= | synonymous_variant | 7/12 | 1 | NM_016169.4 | ENSP00000358918 | P1 | |
SUFU | ENST00000423559.2 | c.849G>A | p.Glu283= | synonymous_variant | 7/10 | 1 | ENSP00000411597 | |||
SUFU | ENST00000369899.6 | c.849G>A | p.Glu283= | synonymous_variant | 7/11 | 1 | ENSP00000358915 | |||
SUFU | ENST00000471000.1 | n.631G>A | non_coding_transcript_exon_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251430Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135894
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461830Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727210
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74274
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 01, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | SUFU: BP4, BP7 - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 23, 2022 | 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. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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