chr1-45340215-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001407071.1(MUTYH):c.-19C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001407071.1 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TOE1 | ENST00000372090 | c.-38G>A | 5_prime_UTR_variant | Exon 1 of 8 | 1 | NM_025077.4 | ENSP00000361162.5 | |||
ENSG00000288208 | ENST00000671898.1 | n.541-5704C>T | intron_variant | Intron 5 of 20 | ENSP00000499896.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461418Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727038
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Gastric cancer;C3272841:Familial adenomatous polyposis 2 Uncertain:1
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Familial adenomatous polyposis 2 Uncertain:1
ClinVar contains an entry for this variant (Variation ID: 480005). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. This sequence change falls in intron 1 of the MUTYH gene. It does not directly change the encoded amino acid sequence of the MUTYH protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. -
Hereditary cancer-predisposing syndrome Uncertain:1
The c.36+4C>T intronic variant results from a C to T substitution 4 nucleotides after coding exon 1 in the MUTYH gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive; however, direct evidence is insufficient at this time (Ambry internal data). 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