Genetic Variant MICA:p.Ser228Ser (chr6-31412017-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001177519.3(MICA):c.684C>T(p.Ser228Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 1,604,280 control chromosomes in the GnomAD database, including 73,757 homozygotes. In-silico tool predicts 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 ( 10062 hom., cov: 31)

Exomes 𝑓: 0.29 ( 63695 hom. )

Consequence

MICA
NM_001177519.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.49

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP7

Synonymous conserved (PhyloP=-2.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3 link	c.684C>T	p.Ser228Ser	synonymous_variant	Exon 4 of 6	ENST00000449934.7	NP_001170990.1	Q96QC4
MICA	NM_001289152.2 link	c.393C>T	p.Ser131Ser	synonymous_variant	Exon 4 of 6		NP_001276081.1	Q96QC4A0A024RCL3
MICA	NM_001289153.2 link	c.393C>T	p.Ser131Ser	synonymous_variant	Exon 4 of 6		NP_001276082.1	Q96QC4A0A024RCL3
MICA	NM_001289154.2 link	c.270C>T	p.Ser90Ser	synonymous_variant	Exon 4 of 6		NP_001276083.1	Q96QC4A0A0G2JJ55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 link	c.684C>T	p.Ser228Ser	synonymous_variant	Exon 4 of 6	1	NM_001177519.3	ENSP00000413079.1		Q96QC4

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53349

AN:

151546

Hom.:

10043

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.317

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.282

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.310

AC:

70761

AN:

228332

Hom.:

13283

AF XY:

0.301

AC XY:

37118

AN XY:

123460

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.433

Gnomad EAS exome

AF:

0.326

Gnomad SAS exome

AF:

0.259

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.285

AC:

414719

AN:

1452616

Hom.:

63695

Cov.:

AF XY:

0.286

AC XY:

206343

AN XY:

722110

show subpopulations

Gnomad4 AFR exome

AF:

0.456

Gnomad4 AMR exome

AF:

0.447

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.305

Gnomad4 SAS exome

AF:

0.299

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.264

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.352

AC:

53414

AN:

151664

Hom.:

10062

Cov.:

AF XY:

0.356

AC XY:

26391

AN XY:

74138

show subpopulations

Gnomad4 AFR

AF:

0.446

Gnomad4 AMR

AF:

0.392

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.317

Gnomad4 SAS

AF:

0.306

Gnomad4 FIN

AF:

0.371

Gnomad4 NFE

AF:

0.282

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.311

Hom.:

2176

Bravo

AF:

0.358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.43

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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