dbSNP rs1051792: MICA:p.Val152Met (chr6-31411200-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001177519.3(MICA):c.454G>A(p.Val152Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 1,612,522 control chromosomes in the GnomAD database, including 74,084 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 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: 𝑓 0.35 ( 10105 hom., cov: 31)

Exomes 𝑓: 0.29 ( 63979 hom. )

Consequence

MICA
NM_001177519.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.139

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3 link	c.454G>A	p.Val152Met	missense_variant	Exon 3 of 6	ENST00000449934.7	NP_001170990.1	Q96QC4
MICA	NM_001289152.2 link	c.163G>A	p.Val55Met	missense_variant	Exon 3 of 6		NP_001276081.1	Q96QC4A0A024RCL3
MICA	NM_001289153.2 link	c.163G>A	p.Val55Met	missense_variant	Exon 3 of 6		NP_001276082.1	Q96QC4A0A024RCL3
MICA	NM_001289154.2 link	c.84-44G>A		intron_variant	Intron 2 of 5		NP_001276083.1	Q96QC4A0A0G2JJ55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 link	c.454G>A	p.Val152Met	missense_variant	Exon 3 of 6	1	NM_001177519.3	ENSP00000413079.1		Q96QC4

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53400

AN:

151504

Hom.:

10086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.443

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.376

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.353

GnomAD3 exomes

AF:

0.337

AC:

83619

AN:

248078

Hom.:

15602

AF XY:

0.329

AC XY:

44360

AN XY:

134664

show subpopulations

Gnomad AFR exome

AF:

0.456

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.341

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.357

Gnomad NFE exome

AF:

0.283

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

AF:

0.287

AC:

419302

AN:

1460900

Hom.:

63979

Cov.:

AF XY:

0.287

AC XY:

208884

AN XY:

726728

show subpopulations

Gnomad4 AFR exome

AF:

0.457

Gnomad4 AMR exome

AF:

0.449

Gnomad4 ASJ exome

AF:

0.457

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.350

Gnomad4 NFE exome

AF:

0.265

Gnomad4 OTH exome

AF:

0.312

GnomAD4 genome

AF:

0.353

AC:

53465

AN:

151622

Hom.:

10105

Cov.:

AF XY:

0.356

AC XY:

26407

AN XY:

74078

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.307

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.283

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.320

Hom.:

3611

Bravo

AF:

0.358

TwinsUK

AF:

0.257

AC:

953

ALSPAC

AF:

0.248

AC:

956

ESP6500AA

AF:

0.419

AC:

580

ESP6500EA

AF:

0.289

AC:

919

ExAC

AF:

0.329

AC:

39732

Asia WGS

AF:

0.367

AC:

1273

AN:

3476

EpiCase

AF:

0.303

EpiControl

AF:

0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.38

Eigen

Benign

-0.79

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0098

MetaRNN

Benign

0.00044

T;T

MetaSVM

Benign

-0.87

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.076

Sift

Benign

0.17

.;T

Sift4G

Benign

0.16

T;T

Polyphen

0.96

.;D

Vest4

0.098

MPC

0.45

ClinPred

0.018

GERP RS

-0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: 9

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over