NM_001040108.2:c.4289_4293delGTCTC
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_ModerateBS2
The NM_001040108.2(MLH3):c.4289_4293delGTCTC(p.Arg1430LeufsTer7) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000868 in 1,612,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001040108.2 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000661 AC: 1AN: 151316Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251454Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461642Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 727146
GnomAD4 genome AF: 0.00000661 AC: 1AN: 151316Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 73968
ClinVar
Submissions by phenotype
Colorectal cancer, hereditary nonpolyposis, type 7 Uncertain:1
This sequence change results in a premature translational stop signal in the MLH3 gene (p.Arg1430Leufs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acids of the MLH3 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH3-related disease. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MLH3 cause disease. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at