rs368383907
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001048174.2(MUTYH):c.366C>T(p.Thr122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,020 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 1 hom. )
Consequence
MUTYH
NM_001048174.2 synonymous
NM_001048174.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.607
Genes affected
MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
Variant 1-45333109-G-A is Benign according to our data. Variant chr1-45333109-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 187674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45333109-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.607 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.450C>T | p.Thr150= | synonymous_variant | 5/16 | ENST00000710952.2 | |
MUTYH | NM_001048174.2 | c.366C>T | p.Thr122= | synonymous_variant | 5/16 | ENST00000456914.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.450C>T | p.Thr150= | synonymous_variant | 5/16 | NM_001128425.2 | |||
MUTYH | ENST00000456914.7 | c.366C>T | p.Thr122= | synonymous_variant | 5/16 | 1 | NM_001048174.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251472Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135908
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GnomAD4 exome AF: 0.0000493 AC: 72AN: 1461886Hom.: 1 Cov.: 34 AF XY: 0.0000550 AC XY: 40AN XY: 727244
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74320
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ClinVar
Significance: Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | MUTYH: BP4, BP7 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Oct 16, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 14, 2020 | This variant is associated with the following publications: (PMID: 16557584) - |
Familial adenomatous polyposis 2 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Feb 05, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 20, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2014 | 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. - |
MUTYH-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 09, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at