chr2-47806642-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_000179.3(MSH6):c.3992G>T(p.Arg1331Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,609,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R1331Q) has been classified as Likely benign.
Frequency
Consequence
NM_000179.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH6 | NM_000179.3 | c.3992G>T | p.Arg1331Leu | missense_variant | 9/10 | ENST00000234420.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH6 | ENST00000234420.11 | c.3992G>T | p.Arg1331Leu | missense_variant | 9/10 | 1 | NM_000179.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151626Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245650Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133152
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1457508Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 725240
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151742Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74124
ClinVar
Submissions by phenotype
Lynch syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Oct 30, 2015 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The p.R1331L variant (also known as c.3992G>T), located in coding exon 9 of the MSH6 gene, results from a G to T substitution at nucleotide position 3992. The arginine at codon 1331 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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 | Jul 06, 2023 | - - |
Hereditary nonpolyposis colorectal neoplasms Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at