chr1-45329310-TG-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate
The NM_001048174.2(MUTYH):c.1561del(p.Gln521SerfsTer22) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. Q521Q) has been classified as Likely benign.
Frequency
Consequence
NM_001048174.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.1645del | p.Gln549SerfsTer22 | frameshift_variant | 16/16 | ENST00000710952.2 | |
MUTYH | NM_001048174.2 | c.1561del | p.Gln521SerfsTer22 | frameshift_variant | 16/16 | ENST00000456914.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.1645del | p.Gln549SerfsTer22 | frameshift_variant | 16/16 | NM_001128425.2 | |||
MUTYH | ENST00000456914.7 | c.1561del | p.Gln521SerfsTer22 | frameshift_variant | 16/16 | 1 | NM_001048174.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461882Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727242
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 19, 2020 | The c.1645delC (p.Q549Sfs*22) variant, located in coding exon 16 of the MUTYH gene causes a translational frameshift and an extension of the protein by 20 amino acids. This alteration occurs at the 3' terminus of theMUTYH gene and is not expected to trigger nonsense-mediated mRNAdecay. A different variant which results in a similarly elongated protein has been detected in a biallelic state in multiple patients with polyposis (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.