2-47806855-TTA-TTATA
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM4
The NM_000179.3(MSH6):c.4081_4082dupTA(p.Ter1361TyrfsTer11) variant causes a frameshift, stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,708 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position has been classified as Likely benign.
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
MSH6
NM_000179.3 frameshift, stop_lost
NM_000179.3 frameshift, stop_lost
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.44
Publications
0 publications found
Genes affected
MSH6 (HGNC:7329): (mutS homolog 6) This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
FBXO11 (HGNC:13590): (F-box protein 11) This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene belongs to the Fbxs class. It can function as an arginine methyltransferase that symmetrically dimethylates arginine residues, and it acts as an adaptor protein to mediate the neddylation of p53, which leads to the suppression of p53 function. This gene is known to be down-regulated in melanocytes from patients with vitiligo, a skin disorder that results in depigmentation. Polymorphisms in this gene are associated with chronic otitis media with effusion and recurrent otitis media (COME/ROM), a hearing loss disorder, and the knockout of the homologous mouse gene results in the deaf mouse mutant Jeff (Jf), a single gene model of otitis media. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2010]
FBXO11 Gene-Disease associations (from GenCC):
- intellectual developmental disorder with dysmorphic facies and behavioral abnormalitiesInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Stoplost variant in NM_000179.3 Downstream stopcodon found after 47 codons.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000179.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MSH6 | NM_000179.3 | MANE Select | c.4081_4082dupTA | p.Ter1361TyrfsTer11 | frameshift stop_lost | Exon 10 of 10 | NP_000170.1 | ||
| MSH6 | NM_001406795.1 | c.4177_4178dupTA | p.Ter1393TyrfsTer11 | frameshift stop_lost | Exon 11 of 11 | NP_001393724.1 | |||
| MSH6 | NM_001406813.1 | c.4087_4088dupTA | p.Ter1363TyrfsTer11 | frameshift stop_lost | Exon 10 of 10 | NP_001393742.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MSH6 | ENST00000234420.11 | TSL:1 MANE Select | c.4081_4082dupTA | p.Ter1361TyrfsTer11 | frameshift stop_lost | Exon 10 of 10 | ENSP00000234420.5 | ||
| MSH6 | ENST00000445503.5 | TSL:1 | n.*3428_*3429dupTA | non_coding_transcript_exon | Exon 9 of 9 | ENSP00000405294.1 | |||
| MSH6 | ENST00000445503.5 | TSL:1 | n.*3428_*3429dupTA | 3_prime_UTR | Exon 9 of 9 | ENSP00000405294.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457708Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 725424 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1457708
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
725424
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33384
American (AMR)
AF:
AC:
0
AN:
44696
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26104
East Asian (EAS)
AF:
AC:
0
AN:
39570
South Asian (SAS)
AF:
AC:
0
AN:
86112
European-Finnish (FIN)
AF:
AC:
0
AN:
53248
Middle Eastern (MID)
AF:
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1108616
Other (OTH)
AF:
AC:
0
AN:
60224
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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