Genetic Variant MICA:p.Gly198Arg (chr6-31411338-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001177519.3(MICA):c.592G>C(p.Gly198Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MICA
NM_001177519.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0290

Publications

65 publications found

Variant links:

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]

MICA links:

ENSG00000288587 (HGNC:):

ENSG00000288587 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11545664).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MICA	NM_001177519.3	MANE Select	c.592G>C	p.Gly198Arg	missense	Exon 3 of 6	NP_001170990.1
MICA	NM_001289152.2		c.301G>C	p.Gly101Arg	missense	Exon 3 of 6	NP_001276081.1
MICA	NM_001289153.2		c.301G>C	p.Gly101Arg	missense	Exon 3 of 6	NP_001276082.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MICA	ENST00000449934.7	TSL:1 MANE Select	c.592G>C	p.Gly198Arg	missense	Exon 3 of 6	ENSP00000413079.1
MICA	ENST00000616296.4	TSL:5	c.301G>C	p.Gly101Arg	missense	Exon 3 of 6	ENSP00000482382.1
MICA	ENST00000674069.1		c.178G>C	p.Gly60Arg	missense	Exon 3 of 6	ENSP00000501157.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000525

AC:

AN:

190540

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1424092

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

705002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32348

American (AMR)

AF:

0.00

AC:

AN:

37812

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25462

East Asian (EAS)

AF:

0.00

AC:

AN:

37340

South Asian (SAS)

AF:

0.00

AC:

AN:

81470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51224

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

9.14e-7

AC:

AN:

1093532

Other (OTH)

AF:

0.00

AC:

AN:

59180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.1

(source)

DANN

Benign

0.69

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0090

M_CAP

Benign

0.0013

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.93

PhyloP100

-0.029

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.039

Sift

Benign

0.21

Sift4G

Benign

0.18

Polyphen

0.19

Vest4

0.14

MutPred

0.64

Gain of MoRF binding (P = 0.0244)

MVP

0.030

MPC

0.15

ClinPred

0.075

GERP RS

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.44

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over