chr2-47801125-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBP6
The NM_000179.3(MSH6):āc.3142C>Gā(p.Gln1048Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1048H) has been classified as Uncertain significance.
Frequency
Consequence
NM_000179.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH6 | NM_000179.3 | c.3142C>G | p.Gln1048Glu | missense_variant | 4/10 | ENST00000234420.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH6 | ENST00000234420.11 | c.3142C>G | p.Gln1048Glu | missense_variant | 4/10 | 1 | NM_000179.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247774Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134420
GnomAD4 exome Cov.: 34
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74428
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 20, 2016 | The p.Q1048E variant (also known as c.3142C>G), located in coding exon 4 of the MSH6 gene, results from a C to G substitution at nucleotide position 3142. The glutamine at codon 1048 is replaced by glutamic acid, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs200492211. Based on data from the 1000 Genomes Project, the G allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.94% (1/106) African-American SW alleles. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, the CoDP in silico tool predicts this alteration to have no impact on molecular function, with a score of 0.002 (Terui H et al. J. Biomed. Sci. 2013;20:25). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Endometrial carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Nov 18, 2023 | - - |
Hereditary nonpolyposis colorectal neoplasms Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at