5-80654689-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002439.5(MSH3):c.-39C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000032 in 1,561,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
MSH3
NM_002439.5 5_prime_UTR
NM_002439.5 5_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.00800
Genes affected
DHFR (HGNC:2861): (dihydrofolate reductase) Dihydrofolate reductase converts dihydrofolate into tetrahydrofolate, a methyl group shuttle required for the de novo synthesis of purines, thymidylic acid, and certain amino acids. While the functional dihydrofolate reductase gene has been mapped to chromosome 5, multiple intronless processed pseudogenes or dihydrofolate reductase-like genes have been identified on separate chromosomes. Dihydrofolate reductase deficiency has been linked to megaloblastic anemia. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
MSH3 (HGNC:7326): (mutS homolog 3) The protein encoded by this gene forms a heterodimer with MSH2 to form MutS beta, part of the post-replicative DNA mismatch repair system. MutS beta initiates mismatch repair by binding to a mismatch and then forming a complex with MutL alpha heterodimer. This gene contains a polymorphic 9 bp tandem repeat sequence in the first exon. The repeat is present 6 times in the reference genome sequence and 3-7 repeats have been reported. Defects in this gene are a cause of susceptibility to endometrial cancer. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DHFR | NM_000791.4 | c.-200G>C | 5_prime_UTR_variant | 1/6 | ENST00000439211.7 | ||
MSH3 | NM_002439.5 | c.-39C>G | 5_prime_UTR_variant | 1/24 | ENST00000265081.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH3 | ENST00000265081.7 | c.-39C>G | 5_prime_UTR_variant | 1/24 | 1 | NM_002439.5 | P2 | ||
DHFR | ENST00000439211.7 | c.-200G>C | 5_prime_UTR_variant | 1/6 | 1 | NM_000791.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151488Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000509 AC: 1AN: 196436Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 110392
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GnomAD4 exome AF: 7.09e-7 AC: 1AN: 1410328Hom.: 0 Cov.: 26 AF XY: 0.00000142 AC XY: 1AN XY: 702454
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GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151488Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 73942
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at