chr1-45333442-C-G
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBP6
The NM_001048174.2(MUTYH):c.235G>C(p.Glu79Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E79G) has been classified as Likely benign.
Frequency
Consequence
NM_001048174.2 missense
Scores
Clinical Significance
Conservation
Publications
- familial adenomatous polyposis 2Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P
- colorectal cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- familial ovarian cancerInheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
- hereditary breast carcinomaInheritance: AD, AR Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000456914.7 | c.235G>C | p.Glu79Gln | missense_variant | Exon 3 of 16 | 1 | NM_001048174.2 | ENSP00000407590.2 | ||
ENSG00000288208 | ENST00000671898.1 | n.823G>C | non_coding_transcript_exon_variant | Exon 7 of 21 | ENSP00000499896.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD2 exomes AF: 0.00000398 AC: 1AN: 251486 AF XY: 0.00000736 show subpopulations
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461882Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727238 show subpopulations
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 2 Uncertain:2
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This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 107 of the MUTYH protein (p.Glu107Gln). This variant is present in population databases (rs773108803, 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: 406863). 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 tolerated. 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
The p.E107Q variant (also known as c.319G>C), located in coding exon 3 of the MUTYH gene, results from a G to C substitution at nucleotide position 319. The glutamic acid at codon 107 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at