rs1367615271
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_000179.3(MSH6):βc.3845_3847delβ(p.Thr1282del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. T1282T) has been classified as Likely benign.
Frequency
Consequence
NM_000179.3 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MSH6 | NM_000179.3 | c.3845_3847del | p.Thr1282del | inframe_deletion | 9/10 | ENST00000234420.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH6 | ENST00000234420.11 | c.3845_3847del | p.Thr1282del | inframe_deletion | 9/10 | 1 | NM_000179.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461786Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727196
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74310
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 07, 2023 | The c.3845_3847delCTA variant (also known as p.T1282del) is located in coding exon 9 of the MSH6 gene. This variant results from an in-frame CTA deletion at nucleotide positions 3845 to 3847. This results in the in-frame deletion of a threonine at codon 1282. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 13, 2019 | - - |
Hereditary nonpolyposis colorectal neoplasms Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 14, 2023 | This variant, c.3845_3847del, results in the deletion of 1 amino acid(s) of the MSH6 protein (p.Thr1282del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. ClinVar contains an entry for this variant (Variation ID: 490010). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at