Variant 6-31410798-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 4P and 6B. PVS1_StrongBP6_ModerateBS2

The NM_001177519.3(MICA):c.325+1G>A variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,558,474 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 35 hom. )

Consequence

MICA
NM_001177519.3 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.25425425 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

BP6

Variant 6-31410798-G-A is Benign according to our data. Variant chr6-31410798-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656400.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MICA	NM_001177519.3 linkuse as main transcript	c.325+1G>A	splice_donor_variant	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2 linkuse as main transcript	c.34+1G>A	splice_donor_variant		NP_001276081.1
MICA	NM_001289153.2 linkuse as main transcript	c.34+1G>A	splice_donor_variant		NP_001276082.1
MICA	NM_001289154.2 linkuse as main transcript	c.83+1G>A	splice_donor_variant		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 linkuse as main transcript	c.325+1G>A		splice_donor_variant		1	NM_001177519.3	ENSP00000413079	P1

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

386

AN:

151934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000775

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00559

Gnomad ASJ

AF:

0.0211

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00270

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00319

AC:

529

AN:

165950

Hom.:

AF XY:

0.00286

AC XY:

251

AN XY:

87810

show subpopulations

Gnomad AFR exome

AF:

0.000786

Gnomad AMR exome

AF:

0.00556

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000173

Gnomad NFE exome

AF:

0.00322

Gnomad OTH exome

AF:

0.00452

GnomAD4 exome

AF:

0.00258

AC:

3622

AN:

1406422

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1709

AN XY:

694480

show subpopulations

Gnomad4 AFR exome

AF:

0.000566

Gnomad4 AMR exome

AF:

0.00553

Gnomad4 ASJ exome

AF:

0.0162

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000219

Gnomad4 NFE exome

AF:

0.00256

Gnomad4 OTH exome

AF:

0.00361

GnomAD4 genome

AF:

0.00255

AC:

387

AN:

152052

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000773

Gnomad4 AMR

AF:

0.00564

Gnomad4 ASJ

AF:

0.0211

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00270

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00316

Hom.:

Bravo

AF:

0.00294

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00346

AC:

ExAC

AF:

0.00172

AC:

192

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

ENSG00000288587: BS2; MICA: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.93

Eigen

Uncertain

0.49

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.66

MutationTaster

Benign

1.0

D;D;D;D

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.77

SpliceAI score (max)

0.60

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.60

Position offset: -1

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