chr6-31412383-T-TG

Variant names:

• chr6-31412383-T-TG
• rs67841474
• NM_001177519.3:c.953dupG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001177519.3(MICA):​c.953dupG​(p.Cys319LeufsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 26)
• Consequence: MICA NM_001177519.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659
• Publications: 20 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	NM_001177519.3	MANE Select	c.953dupG	p.Cys319LeufsTer28	frameshift	Exon 5 of 6	NP_001170990.1
	MICA	NM_001289152.2		c.662dupG	p.Cys222LeufsTer28	frameshift	Exon 5 of 6	NP_001276081.1
	MICA	NM_001289153.2		c.662dupG	p.Cys222LeufsTer28	frameshift	Exon 5 of 6	NP_001276082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICA	ENST00000449934.7	TSL:1 MANE Select	c.953dupG	p.Cys319LeufsTer28	frameshift	Exon 5 of 6	ENSP00000413079.1
	MICA	ENST00000616296.4	TSL:5	c.662dupG	p.Cys222LeufsTer28	frameshift	Exon 5 of 6	ENSP00000482382.1
	MICA	ENST00000421350.1	TSL:5	c.626dupG	p.Cys210LeufsTer28	frameshift	Exon 4 of 5	ENSP00000402410.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.66

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

Other links and lift over

dbSNP: rs67841474; hg19: chr6-31380160;