6-31412384-G-GCTGCTGCTGCTGCTGCTGCT
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_001177519.3(MICA):c.952_953insCTGCTGCTGCTGCTGCTGCT(p.Gly318AlafsTer75) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000037 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MICA
NM_001177519.3 frameshift
NM_001177519.3 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.641
Publications
18 publications found
Genes affected
MICA (HGNC:7090): (MHC class I polypeptide-related sequence A) This gene encodes the highly polymorphic major histocompatability complex class I chain-related protein A. The protein product is expressed on the cell surface, although unlike canonical class I molecules it does not seem to associate with beta-2-microglobulin. It is a ligand for the NKG2-D type II integral membrane protein receptor. The protein functions as a stress-induced antigen that is broadly recognized by intestinal epithelial gamma delta T cells. Variations in this gene have been associated with susceptibility to psoriasis 1 and psoriatic arthritis, and the shedding of MICA-related antibodies and ligands is involved in the progression from monoclonal gammopathy of undetermined significance to multiple myeloma. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001177519.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MICA | MANE Select | c.952_953insCTGCTGCTGCTGCTGCTGCT | p.Gly318AlafsTer75 | frameshift | Exon 5 of 6 | NP_001170990.1 | Q96QC4 | ||
| MICA | c.661_662insCTGCTGCTGCTGCTGCTGCT | p.Gly221AlafsTer75 | frameshift | Exon 5 of 6 | NP_001276081.1 | A0A024RCL3 | |||
| MICA | c.661_662insCTGCTGCTGCTGCTGCTGCT | p.Gly221AlafsTer75 | frameshift | Exon 5 of 6 | NP_001276082.1 | A0A024RCL3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MICA | TSL:1 MANE Select | c.952_953insCTGCTGCTGCTGCTGCTGCT | p.Gly318AlafsTer75 | frameshift | Exon 5 of 6 | ENSP00000413079.1 | Q96QC4 | ||
| MICA | c.697_698insCTGCTGCTGCTGCTGCTGCT | p.Gly233AlafsTer75 | frameshift | Exon 4 of 5 | ENSP00000562179.1 | ||||
| MICA | TSL:5 | c.661_662insCTGCTGCTGCTGCTGCTGCT | p.Gly221AlafsTer75 | frameshift | Exon 5 of 6 | ENSP00000482382.1 | A0A024RCL3 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 120862Hom.: 0 Cov.: 0
GnomAD3 genomes
AF:
AC:
0
AN:
120862
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000371 AC: 4AN: 1078846Hom.: 0 Cov.: 35 AF XY: 0.00000187 AC XY: 1AN XY: 534690 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
4
AN:
1078846
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
534690
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
30192
American (AMR)
AF:
AC:
0
AN:
30014
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
21796
East Asian (EAS)
AF:
AC:
0
AN:
23478
South Asian (SAS)
AF:
AC:
0
AN:
65974
European-Finnish (FIN)
AF:
AC:
0
AN:
33764
Middle Eastern (MID)
AF:
AC:
0
AN:
4828
European-Non Finnish (NFE)
AF:
AC:
3
AN:
823124
Other (OTH)
AF:
AC:
0
AN:
45676
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00383038), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
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10
<30
30-35
35-40
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70-75
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>80
Age
GnomAD4 genome 0.00 AC: 0AN: 120862Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 58666
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
120862
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
58666
African (AFR)
AF:
AC:
0
AN:
37864
American (AMR)
AF:
AC:
0
AN:
12414
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3034
East Asian (EAS)
AF:
AC:
0
AN:
2846
South Asian (SAS)
AF:
AC:
0
AN:
3830
European-Finnish (FIN)
AF:
AC:
0
AN:
7206
Middle Eastern (MID)
AF:
AC:
0
AN:
256
European-Non Finnish (NFE)
AF:
AC:
0
AN:
50914
Other (OTH)
AF:
AC:
0
AN:
1718
Alfa
AF:
Hom.:
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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