rs1484161045
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001040108.2(MLH3):āc.443T>Gā(p.Val148Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V148A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001040108.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MLH3 | NM_001040108.2 | c.443T>G | p.Val148Gly | missense_variant | 2/13 | ENST00000355774.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLH3 | ENST00000355774.7 | c.443T>G | p.Val148Gly | missense_variant | 2/13 | 5 | NM_001040108.2 | P1 | |
MLH3 | ENST00000380968.6 | c.443T>G | p.Val148Gly | missense_variant | 2/12 | 1 | |||
MLH3 | ENST00000556257.5 | c.443T>G | p.Val148Gly | missense_variant | 2/7 | 5 | |||
MLH3 | ENST00000553263.1 | c.443T>G | p.Val148Gly | missense_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251446Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135900
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461878Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3AN XY: 727242
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | The p.V148G variant (also known as c.443T>G), located in coding exon 1 of the MLH3 gene, results from a T to G substitution at nucleotide position 443. The valine at codon 148 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Colorectal cancer, hereditary nonpolyposis, type 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 07, 2023 | This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 148 of the MLH3 protein (p.Val148Gly). ClinVar contains an entry for this variant (Variation ID: 544287). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at