chr1-45331665-G-C
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PM1PM2BP4_ModerateBP6_Moderate
The NM_001048174.2(MUTYH):c.1098C>G(p.Asn366Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N366D) has been classified as Uncertain significance.
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 0 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MUTYH | ENST00000456914.7 | c.1098C>G | p.Asn366Lys | missense_variant | Exon 12 of 16 | 1 | NM_001048174.2 | ENSP00000407590.2 | ||
ENSG00000288208 | ENST00000671898.1 | n.1686C>G | non_coding_transcript_exon_variant | Exon 16 of 21 | ENSP00000499896.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.N394K variant (also known as c.1182C>G), located in coding exon 12 of the MUTYH gene, results from a C to G substitution at nucleotide position 1182. The asparagine at codon 394 is replaced by lysine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. 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