rs1553129638
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001048174.2(MUTYH):c.337del(p.Gln113ArgfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
MUTYH
NM_001048174.2 frameshift
NM_001048174.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.46
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-45333137-TG-T is Pathogenic according to our data. Variant chr1-45333137-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 464719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45333137-TG-T is described in Lovd as [Likely_pathogenic]. Variant chr1-45333137-TG-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.421del | p.Gln141ArgfsTer5 | frameshift_variant | 5/16 | ENST00000710952.2 | |
MUTYH | NM_001048174.2 | c.337del | p.Gln113ArgfsTer5 | frameshift_variant | 5/16 | ENST00000456914.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.421del | p.Gln141ArgfsTer5 | frameshift_variant | 5/16 | NM_001128425.2 | |||
MUTYH | ENST00000456914.7 | c.337del | p.Gln113ArgfsTer5 | frameshift_variant | 5/16 | 1 | NM_001048174.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial adenomatous polyposis 2 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | Jul 02, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 26, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MUTYH are known to be pathogenic. This particular variant has been reported as compound heterozygous with other pathogenic variants in MUTYH in individuals with Muir–Torre syndrome (PMID: 16207212), attenuated polyposis (PMID: 22865608), and colorectal adenomas (PMID: 22773231). This variant is also known as 379delC. This sequence change deletes 1 nucleotide in exon 5 of the MUTYH mRNA (c.421delC), causing a frameshift at codon 141. This creates a premature translational stop signal (p.Gln141Argfs*5) and is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at