Variant 6-31411298-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001177519.3(MICA):c.552T>G(p.His184Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,454,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MICA
NM_001177519.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0650

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:

MICA (HGNC:):

MICA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022427946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICA	NM_001177519.3 linkuse as main transcript	c.552T>G	p.His184Gln	missense_variant	3/6	ENST00000449934.7	NP_001170990.1	Q96QC4
MICA	NM_001289152.2 linkuse as main transcript	c.261T>G	p.His87Gln	missense_variant	3/6		NP_001276081.1	Q96QC4A0A024RCL3
MICA	NM_001289153.2 linkuse as main transcript	c.261T>G	p.His87Gln	missense_variant	3/6		NP_001276082.1	Q96QC4A0A024RCL3
MICA	NM_001289154.2 linkuse as main transcript	c.138T>G	p.His46Gln	missense_variant	3/6		NP_001276083.1	Q96QC4A0A0G2JJ55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 linkuse as main transcript	c.552T>G	p.His184Gln	missense_variant	3/6	1	NM_001177519.3	ENSP00000413079.1		Q96QC4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000851

AC:

AN:

234956

Hom.:

AF XY:

0.00000785

AC XY:

AN XY:

127358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000942

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1454454

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

722930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000235

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000487

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.083

DANN

Benign

0.36

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.00011

M_CAP

Benign

0.0011

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.31

PROVEAN

Benign

1.6

.;N

REVEL

Benign

0.011

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.010

.;B

Vest4

0.071

MutPred

0.35

.;Loss of sheet (P = 0.0181);

MVP

0.014

MPC

0.11

ClinPred

0.025

GERP RS

-0.47

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over