chr6-31412063-G-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001177519.3(MICA):c.730G>C(p.Val244Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,032 control chromosomes in the GnomAD database, including 700 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.015 ( 68 hom., cov: 32)
Exomes 𝑓: 0.014 ( 632 hom. )
Consequence
MICA
NM_001177519.3 missense
NM_001177519.3 missense
Scores
11
Clinical Significance
Conservation
PhyloP100: 0.295
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 made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0029048324).
BP6
?
Variant 6-31412063-G-C is Benign according to our data. Variant chr6-31412063-G-C is described in ClinVar as [Benign]. Clinvar id is 218532.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0807 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MICA | NM_001177519.3 | c.730G>C | p.Val244Leu | missense_variant | 4/6 | ENST00000449934.7 | |
MICA | NM_001289152.2 | c.439G>C | p.Val147Leu | missense_variant | 4/6 | ||
MICA | NM_001289153.2 | c.439G>C | p.Val147Leu | missense_variant | 4/6 | ||
MICA | NM_001289154.2 | c.316G>C | p.Val106Leu | missense_variant | 4/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MICA | ENST00000449934.7 | c.730G>C | p.Val244Leu | missense_variant | 4/6 | 1 | NM_001177519.3 | P1 | |
MICA | ENST00000616296.4 | c.439G>C | p.Val147Leu | missense_variant | 4/6 | 5 | |||
MICA | ENST00000421350.1 | c.403G>C | p.Val135Leu | missense_variant | 3/5 | 5 | |||
MICA | ENST00000674069.1 | c.316G>C | p.Val106Leu | missense_variant | 4/6 |
Frequencies
GnomAD3 genomes ? AF: 0.0147 AC: 2233AN: 151848Hom.: 68 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0213 AC: 5266AN: 246816Hom.: 240 AF XY: 0.0230 AC XY: 3080AN XY: 134032
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GnomAD4 exome AF: 0.0144 AC: 21030AN: 1461066Hom.: 632 Cov.: 85 AF XY: 0.0155 AC XY: 11290AN XY: 726808
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GnomAD4 genome ? AF: 0.0147 AC: 2229AN: 151966Hom.: 68 Cov.: 32 AF XY: 0.0149 AC XY: 1106AN XY: 74292
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ESP6500AA
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Asia WGS
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Apr 17, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
Sift4G
Benign
T;T;T
Polyphen
0.036
.;B;.
Vest4
MutPred
0.33
.;Loss of MoRF binding (P = 0.1371);.;
MPC
0.10
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at