rs760782238
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM4BP6
The NM_000179.3(MSH6):c.4064_*23dup variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,460,250 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L1354L) has been classified as Likely benign.
Frequency
Consequence
NM_000179.3 stop_gained, frameshift
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.4064_*23dup | stop_gained, frameshift_variant | 10/10 | ENST00000234420.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSH6 | ENST00000234420.11 | c.4064_*23dup | stop_gained, frameshift_variant | 10/10 | 1 | NM_000179.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 4AN: 149478Hom.: 0 Cov.: 31 FAILED QC
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 250978Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135640
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1460250Hom.: 1 Cov.: 32 AF XY: 0.0000468 AC XY: 34AN XY: 726468
GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000267 AC: 4AN: 149580Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1AN XY: 72740
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jul 21, 2023 | To the best of our knowledge, this variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00036 (11/30512 chromosomes in South Asian subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 26, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at