chr3-36993378-GA-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000413740.2(MLH1):c.-167del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,274 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MLH1
ENST00000413740.2 5_prime_UTR
ENST00000413740.2 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.223
Genes affected
MLH1 (HGNC:7127): (mutL homolog 1) The protein encoded by this gene can heterodimerize with mismatch repair endonuclease PMS2 to form MutL alpha, part of the DNA mismatch repair system. When MutL alpha is bound by MutS beta and some accessory proteins, the PMS2 subunit of MutL alpha introduces a single-strand break near DNA mismatches, providing an entry point for exonuclease degradation. The encoded protein is also involved in DNA damage signaling and can heterodimerize with DNA mismatch repair protein MLH3 to form MutL gamma, which is involved in meiosis. This gene was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MLH1 | ENST00000413740.2 | c.-167del | 5_prime_UTR_variant | 1/15 | 1 | ||||
MLH1 | ENST00000536378.5 | c.-799del | 5_prime_UTR_variant | 1/18 | 2 | ||||
MLH1 | ENST00000673673.2 | c.-167del | 5_prime_UTR_variant | 1/18 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 33
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GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 670580Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0AN XY: 354186
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Data not reliable, filtered out with message: AC0;AS_VQSR
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152274Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74400
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Colorectal cancer, hereditary nonpolyposis, type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 08, 2023 | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at