rs33010
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_002439.5(MSH3):c.2543+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 660,196 control chromosomes in the GnomAD database, including 239,146 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.85 ( 54469 hom., cov: 33)
Exomes 𝑓: 0.85 ( 184677 hom. )
Consequence
MSH3
NM_002439.5 intron
NM_002439.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.441
Genes affected
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 Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 5-80787812-G-A is Benign according to our data. Variant chr5-80787812-G-A is described in ClinVar as [Benign]. Clinvar id is 1251794.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH3 | NM_002439.5 | c.2543+140G>A | intron_variant | ENST00000265081.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH3 | ENST00000265081.7 | c.2543+140G>A | intron_variant | 1 | NM_002439.5 | P2 | |||
MSH3 | ENST00000658259.1 | c.2375+140G>A | intron_variant | A2 | |||||
MSH3 | ENST00000667069.1 | c.2348+140G>A | intron_variant | ||||||
MSH3 | ENST00000670357.1 | c.2543+140G>A | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.846 AC: 128652AN: 152142Hom.: 54420 Cov.: 33
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GnomAD4 exome AF: 0.851 AC: 432374AN: 507936Hom.: 184677 AF XY: 0.851 AC XY: 233362AN XY: 274088
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GnomAD4 genome ? AF: 0.846 AC: 128758AN: 152260Hom.: 54469 Cov.: 33 AF XY: 0.849 AC XY: 63192AN XY: 74436
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 22, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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