2-47783190-G-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000179.3(MSH6):c.-44G>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 0.00000137 in 1,455,514 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_000179.3 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
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MSH6 | NM_000179.3 | c.-44G>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 10 | ENST00000234420.11 | NP_000170.1 | ||
MSH6 | NM_000179.3 | c.-44G>T | 5_prime_UTR_variant | Exon 1 of 10 | ENST00000234420.11 | NP_000170.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MSH6 | ENST00000234420 | c.-44G>T | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 10 | 1 | NM_000179.3 | ENSP00000234420.5 | |||
MSH6 | ENST00000234420 | c.-44G>T | 5_prime_UTR_variant | Exon 1 of 10 | 1 | NM_000179.3 | ENSP00000234420.5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000417 AC: 1AN: 239892Hom.: 0 AF XY: 0.00000761 AC XY: 1AN XY: 131406
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1455514Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 724220
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
This variant is denoted MSH6 c.-44G>T, and describes a nucleotide substitution 44 base pairs upstream of the MSH6 ATG translational start site in the 5' untranslated region (UTR). The surrounding sequence, with the base that is substituted in braces, is TTTA[G/T]GAGC. This variant has not been published to our knowledge. MSH6 c.-44G>T 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. This substitution is not tolerated in evolution and it occurs at a position that is conserved in mammals. Although MSH6 c.-44G>T does not affect the usual start codon or the Kozak translational consensus sequence, it does create a new in-frame ATG start codon. Since the creation of this new start codon may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider MSH6 c.-44G>T to be a variant of uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at