6-31412384-G-GCTGCTGCTGCTGCT

Variant names:

• chr6-31412384-G-GCTGCTGCTGCTGCT
• rs41293539
• NM_001177519.3:c.952_953insCTGCTGCTGCTGCT

Variant summary

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

The NM_001177519.3(MICA):​c.952_953insCTGCTGCTGCTGCT​(p.Gly318AlafsTer73) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.00022 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00020 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: MICA NM_001177519.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641
• Publications: 18 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 0 ACMG points.

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.952_953insCTGCTGCTGCTGCT	p.Gly318AlafsTer73	frameshift	Exon 5 of 6	NP_001170990.1	Q96QC4
	MICA	NM_001289152.2		c.661_662insCTGCTGCTGCTGCT	p.Gly221AlafsTer73	frameshift	Exon 5 of 6	NP_001276081.1	A0A024RCL3
	MICA	NM_001289153.2		c.661_662insCTGCTGCTGCTGCT	p.Gly221AlafsTer73	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.952_953insCTGCTGCTGCTGCT	p.Gly318AlafsTer73	frameshift	Exon 5 of 6	ENSP00000413079.1	Q96QC4
	MICA	ENST00000892120.1		c.697_698insCTGCTGCTGCTGCT	p.Gly233AlafsTer73	frameshift	Exon 4 of 5	ENSP00000562179.1
	MICA	ENST00000616296.4	TSL:5	c.661_662insCTGCTGCTGCTGCT	p.Gly221AlafsTer73	frameshift	Exon 5 of 6	ENSP00000482382.1	A0A024RCL3

Frequencies

GnomAD3 genomes AF: 0.000215 AC: 26 AN: 120862 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000806

Gnomad ASJ AF: 0.000659

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000236

Gnomad OTH AF: 0.000582

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000204 AC: 220 AN: 1078826 Hom.: 2 Cov.: 35 AF XY: 0.000200 AC XY: 107 AN XY: 534680

African (AFR) AF: 0.000364 AC: 11 AN: 30188

American (AMR) AF: 0.0000666 AC: 2 AN: 30014

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 20 AN: 21794

East Asian (EAS) AF: 0.0000426 AC: 1 AN: 23478

South Asian (SAS) AF: 0.0000455 AC: 3 AN: 65974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33764

Middle Eastern (MID) AF: 0.000207 AC: 1 AN: 4826

European-Non Finnish (NFE) AF: 0.000211 AC: 174 AN: 823114

Other (OTH) AF: 0.000175 AC: 8 AN: 45674

GnomAD4 genome AF: 0.000215 AC: 26 AN: 120862 Hom.: 1 Cov.: 0 AF XY: 0.000205 AC XY: 12 AN XY: 58666

African (AFR) AF: 0.000264 AC: 10 AN: 37864

American (AMR) AF: 0.0000806 AC: 1 AN: 12414

Ashkenazi Jewish (ASJ) AF: 0.000659 AC: 2 AN: 3034

East Asian (EAS) AF: 0.00 AC: 0 AN: 2846

South Asian (SAS) AF: 0.00 AC: 0 AN: 3830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7206

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.000236 AC: 12 AN: 50914

Other (OTH) AF: 0.000582 AC: 1 AN: 1718

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.64
Mutation Taster		=189/11	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41293539; hg19: chr6-31380161;