rs1677658
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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.237+76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 867,144 control chromosomes in the GnomAD database, including 10,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.12 ( 1211 hom., cov: 30)
Exomes 𝑓: 0.15 ( 9518 hom. )
Consequence
MSH3
NM_002439.5 intron
NM_002439.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0510
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=-0.76).
BP6
?
Variant 5-80655040-G-T is Benign according to our data. Variant chr5-80655040-G-T is described in ClinVar as [Benign]. Clinvar id is 1261132.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH3 | NM_002439.5 | c.237+76G>T | intron_variant | ENST00000265081.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH3 | ENST00000265081.7 | c.237+76G>T | intron_variant | 1 | NM_002439.5 | P2 | |||
MSH3 | ENST00000667069.1 | c.237+76G>T | intron_variant | ||||||
MSH3 | ENST00000670357.1 | c.237+76G>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.118 AC: 17873AN: 151624Hom.: 1211 Cov.: 30
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GnomAD4 exome AF: 0.146 AC: 104802AN: 715412Hom.: 9518 Cov.: 10 AF XY: 0.149 AC XY: 53990AN XY: 362548
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GnomAD4 genome ? AF: 0.118 AC: 17865AN: 151732Hom.: 1211 Cov.: 30 AF XY: 0.116 AC XY: 8584AN XY: 74154
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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
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at