rs587782132
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM5
The ENST00000456914.7(MUTYH):c.398A>T(p.Asp133Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,848 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. D133H) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000456914.7 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MUTYH | NM_001128425.2 | c.482A>T | p.Asp161Val | missense_variant | 6/16 | ENST00000710952.2 | NP_001121897.1 | |
MUTYH | NM_001048174.2 | c.398A>T | p.Asp133Val | missense_variant | 6/16 | ENST00000456914.7 | NP_001041639.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000710952.2 | c.482A>T | p.Asp161Val | missense_variant | 6/16 | NM_001128425.2 | ENSP00000518552 | |||
MUTYH | ENST00000456914.7 | c.398A>T | p.Asp133Val | missense_variant | 6/16 | 1 | NM_001048174.2 | ENSP00000407590 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250400Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135352
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461848Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727228
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 08, 2023 | The p.D161V variant (also known as c.482A>T), located in coding exon 6 of the MUTYH gene, results from an A to T substitution at nucleotide position 482. The aspartic acid at codon 161 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 18, 2021 | This missense variant replaces aspartic acid with valine at codon 161 of the MUTYH protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250400 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Familial adenomatous polyposis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 11, 2024 | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 161 of the MUTYH protein (p.Asp161Val). This variant is present in population databases (rs587782132, gnomAD 0.003%). 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: 141948). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at