1-45332195-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_001048174.2(MUTYH):c.820G>A(p.Val274Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V274L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001048174.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.904G>A | p.Val302Met | missense_variant | 10/16 | ENST00000710952.2 | |
MUTYH | NM_001048174.2 | c.820G>A | p.Val274Met | missense_variant | 10/16 | ENST00000456914.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.904G>A | p.Val302Met | missense_variant | 10/16 | NM_001128425.2 | |||
MUTYH | ENST00000456914.7 | c.820G>A | p.Val274Met | missense_variant | 10/16 | 1 | NM_001048174.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251236Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135860
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461876Hom.: 0 Cov.: 36 AF XY: 0.00000275 AC XY: 2AN XY: 727234
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 21, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 302 of the MUTYH protein (p.Val302Met). This variant is present in population databases (rs760889663, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 566388). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2024 | The p.V302M variant (also known as c.904G>A), located in coding exon 10 of the MUTYH gene, results from a G to A substitution at nucleotide position 904. The valine at codon 302 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at