1-45340199-G-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_025077.4(TOE1):c.-54G>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 0.0000799 in 1,613,538 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_025077.4 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TOE1 | ENST00000372090 | c.-54G>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 8 | 1 | NM_025077.4 | ENSP00000361162.5 | |||
TOE1 | ENST00000372090 | c.-54G>T | 5_prime_UTR_variant | Exon 1 of 8 | 1 | NM_025077.4 | ENSP00000361162.5 | |||
ENSG00000288208 | ENST00000671898.1 | n.541-5688C>A | intron_variant | Intron 5 of 20 | ENSP00000499896.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152234Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000149 AC: 37AN: 248508Hom.: 0 AF XY: 0.000222 AC XY: 30AN XY: 135058
GnomAD4 exome AF: 0.0000814 AC: 119AN: 1461186Hom.: 0 Cov.: 33 AF XY: 0.000131 AC XY: 95AN XY: 726906
GnomAD4 genome AF: 0.0000656 AC: 10AN: 152352Hom.: 1 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74506
ClinVar
Submissions by phenotype
Familial adenomatous polyposis 2 Uncertain:1Benign:1
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not provided Uncertain:1
This variant is denoted MUTYH c.36+20C>A or IVS1+20C>A and consists of a C>A nucleotide substitution at the +20 position of intron 1 of the MUTYH gene. Multiple in silico models predict this variant to create a cryptic donor site in intron 1, and lead to abnormal splicing. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MUTYH c.36+20C>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The cytosine (C) nucleotide that is altered is not conserved across species. Based on currently available information, it is unclear whether MUTYH c.36+20C>A is pathogenic or benign. We consider it to be a variant of uncertain significance. -
Hereditary cancer-predisposing syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at