rs138201170

Variant names:

• chr6-31412380-TGCTG-T
• rs138201170
• NM_001177519.3:c.953_956delGCTG

Your query was ambiguous. Multiple possible variants found:

• chr6-31412380-TGCTG-T
• chr6-31412380-TGCTG-TGCTGGCTG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001177519.3(MICA):​c.953_956delGCTG​(p.Gly318AlafsTer67) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,527,462 control chromosomes in the GnomAD database, including 9,654 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.15 (946 hom., cov: 20)
  • Exomes 𝑓: 0.11 (8708 hom.)
• Consequence: MICA NM_001177519.3 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.131
• Publications: 19 publications found

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]

ENSG00000288587 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-31412380-TGCTG-T is Benign according to our data. Variant chr6-31412380-TGCTG-T is described in ClinVar as Benign. ClinVar VariationId is 403086.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177519.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	NM_001177519.3	MANE Select	c.953_956delGCTG	p.Gly318AlafsTer67	frameshift	Exon 5 of 6	NP_001170990.1	Q96QC4
	MICA	NM_001289152.2		c.662_665delGCTG	p.Gly221AlafsTer67	frameshift	Exon 5 of 6	NP_001276081.1	A0A024RCL3
	MICA	NM_001289153.2		c.662_665delGCTG	p.Gly221AlafsTer67	frameshift	Exon 5 of 6	NP_001276082.1	A0A024RCL3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	ENST00000449934.7	TSL:1 MANE Select	c.953_956delGCTG	p.Gly318AlafsTer67	frameshift	Exon 5 of 6	ENSP00000413079.1	Q96QC4
	MICA	ENST00000892120.1		c.698_701delGCTG	p.Gly233AlafsTer67	frameshift	Exon 4 of 5	ENSP00000562179.1
	MICA	ENST00000616296.4	TSL:5	c.662_665delGCTG	p.Gly221AlafsTer67	frameshift	Exon 5 of 6	ENSP00000482382.1	A0A024RCL3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 15660 AN: 102830 Hom.: 939 Cov.: 20

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.158 AC: 17598 AN: 111472 AF XY: 0.156

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.231

Gnomad FIN exome AF: 0.174

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.177

GnomAD4 exome AF: 0.106 AC: 151295 AN: 1424570 Hom.: 8708 AF XY: 0.106 AC XY: 74757 AN XY: 705794

African (AFR) AF: 0.0763 AC: 2473 AN: 32404

American (AMR) AF: 0.0717 AC: 2694 AN: 37570

Ashkenazi Jewish (ASJ) AF: 0.0818 AC: 2084 AN: 25466

East Asian (EAS) AF: 0.140 AC: 5307 AN: 37946

South Asian (SAS) AF: 0.0717 AC: 5895 AN: 82196

European-Finnish (FIN) AF: 0.138 AC: 7074 AN: 51194

Middle Eastern (MID) AF: 0.113 AC: 648 AN: 5724

European-Non Finnish (NFE) AF: 0.109 AC: 118981 AN: 1093016

Other (OTH) AF: 0.104 AC: 6139 AN: 59054

GnomAD4 genome AF: 0.152 AC: 15683 AN: 102892 Hom.: 946 Cov.: 20 AF XY: 0.157 AC XY: 7771 AN XY: 49540

African (AFR) AF: 0.144 AC: 3408 AN: 23650

American (AMR) AF: 0.166 AC: 1220 AN: 7362

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 264 AN: 1506

East Asian (EAS) AF: 0.252 AC: 738 AN: 2926

South Asian (SAS) AF: 0.169 AC: 370 AN: 2194

European-Finnish (FIN) AF: 0.176 AC: 1440 AN: 8190

Middle Eastern (MID) AF: 0.227 AC: 35 AN: 154

European-Non Finnish (NFE) AF: 0.144 AC: 7911 AN: 54948

Other (OTH) AF: 0.177 AC: 221 AN: 1252

Alfa AF: 0.103 Hom.: 68

Bravo AF: 0.0981

Asia WGS AF: 0.263 AC: 571 AN: 2178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13
Mutation Taster		=193/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs138201170; hg19: chr6-31380157; COSMIC: COSV69826357;