Variant chr6-31412383-TG-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001177519.3(MICA):c.953del(p.Gly318AlafsTer68) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,256,808 control chromosomes in the GnomAD database, including 14,129 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.20 ( 1348 hom., cov: 26)

Exomes 𝑓: 0.14 ( 12781 hom. )

Consequence

MICA
NM_001177519.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.659

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MICA	NM_001177519.3 linkuse as main transcript	c.953del	p.Gly318AlafsTer68	frameshift_variant	5/6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2 linkuse as main transcript	c.662del	p.Gly221AlafsTer68	frameshift_variant	5/6		NP_001276081.1
MICA	NM_001289153.2 linkuse as main transcript	c.662del	p.Gly221AlafsTer68	frameshift_variant	5/6		NP_001276082.1
MICA	NM_001289154.2 linkuse as main transcript	c.539del	p.Gly180AlafsTer68	frameshift_variant	5/6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MICA	ENST00000449934.7 linkuse as main transcript	c.953del	p.Gly318AlafsTer68	frameshift_variant	5/6	1	NM_001177519.3	ENSP00000413079	P1
MICA	ENST00000616296.4 linkuse as main transcript	c.662del	p.Gly221AlafsTer68	frameshift_variant	5/6	5		ENSP00000482382
MICA	ENST00000421350.1 linkuse as main transcript	c.626del	p.Gly209AlafsTer68	frameshift_variant	4/5	5		ENSP00000402410
MICA	ENST00000674069.1 linkuse as main transcript	c.539del	p.Gly180AlafsTer68	frameshift_variant	5/6			ENSP00000501157

Frequencies

GnomAD3 genomes

AF:

0.195

AC:

16232

AN:

83068

Hom.:

1342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0746

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.328

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.212

AC:

29748

AN:

140244

Hom.:

3701

AF XY:

0.210

AC XY:

15790

AN XY:

75368

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.346

Gnomad ASJ exome

AF:

0.243

Gnomad EAS exome

AF:

0.395

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.143

Gnomad OTH exome

AF:

0.207

GnomAD4 exome

AF:

0.142

AC:

166973

AN:

1173710

Hom.:

12781

Cov.:

AF XY:

0.145

AC XY:

84310

AN XY:

581660

show subpopulations

Gnomad4 AFR exome

AF:

0.0271

Gnomad4 AMR exome

AF:

0.237

Gnomad4 ASJ exome

AF:

0.172

Gnomad4 EAS exome

AF:

0.380

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.208

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.195

AC:

16239

AN:

83098

Hom.:

1348

Cov.:

AF XY:

0.209

AC XY:

8460

AN XY:

40476

show subpopulations

Gnomad4 AFR

AF:

0.0745

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.312

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.377

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.0986

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over