rs1206693577
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000179.3(MSH6):āc.2531T>Cā(p.Met844Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M844I) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH6 | NM_000179.3 | c.2531T>C | p.Met844Thr | missense_variant | 4/10 | ENST00000234420.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH6 | ENST00000234420.11 | c.2531T>C | p.Met844Thr | missense_variant | 4/10 | 1 | NM_000179.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460906Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726802
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74328
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 25, 2023 | The p.M844T variant (also known as c.2531T>C), located in coding exon 4 of the MSH6 gene, results from a T to C substitution at nucleotide position 2531. The methionine at codon 844 is replaced by threonine, an amino acid with similar properties. This alteration was detected in 1/59 unrelated families from Singapore who met Amsterdam I or II criteria for Lynch syndrome, and it was classified as a variant of uncertain significance (Liu Y et al. PLoS ONE, 2014 Apr;9:e94170). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at