chr3-37025632-T-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_000249.4(MLH1):c.1039-5T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000249.4 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 1AN: 136976Hom.: 0 Cov.: 26 FAILED QC
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00133 AC: 1299AN: 979512Hom.: 0 Cov.: 21 AF XY: 0.00125 AC XY: 612AN XY: 490682
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000730 AC: 1AN: 137012Hom.: 0 Cov.: 26 AF XY: 0.0000152 AC XY: 1AN XY: 65962
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The c.1039-5T>A intronic variant results from a T to A substitution 5 nucleotides upstream from coding exon 12 in the MLH1 gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.