rs147021156
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001040108.2(MLH3):c.2670G>A(p.Met890Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,614,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001040108.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MLH3 | NM_001040108.2 | c.2670G>A | p.Met890Ile | missense_variant | 2/13 | ENST00000355774.7 | NP_001035197.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MLH3 | ENST00000355774.7 | c.2670G>A | p.Met890Ile | missense_variant | 2/13 | 5 | NM_001040108.2 | ENSP00000348020 | P1 | |
MLH3 | ENST00000380968.6 | c.2670G>A | p.Met890Ile | missense_variant | 2/12 | 1 | ENSP00000370355 | |||
MLH3 | ENST00000556257.5 | c.2670G>A | p.Met890Ile | missense_variant | 2/7 | 5 | ENSP00000451540 | |||
MLH3 | ENST00000555671.1 | n.216G>A | non_coding_transcript_exon_variant | 1/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000880 AC: 134AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000175 AC: 44AN: 251214Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135770
GnomAD4 exome AF: 0.0000698 AC: 102AN: 1461828Hom.: 0 Cov.: 34 AF XY: 0.0000550 AC XY: 40AN XY: 727216
GnomAD4 genome AF: 0.000880 AC: 134AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.000966 AC XY: 72AN XY: 74500
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 30, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Colorectal cancer, hereditary nonpolyposis, type 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 10, 2024 | - - |
MLH3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 10, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at