6-31412384-G-GCTGCTGCTGCTGCTGCT

Variant names:

• chr6-31412384-G-GCTGCTGCTGCTGCTGCT
• rs41293539
• NM_001177519.3:c.952_953insCTGCTGCTGCTGCTGCT

Variant summary

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

The NM_001177519.3(MICA):​c.952_953insCTGCTGCTGCTGCTGCT​(p.Gly318AlafsTer74) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000927 in 1,078,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 0)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.952_953insCTGCTGCTGCTGCTGCT	p.Gly318AlafsTer74	frameshift_variant	Exon 5 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.661_662insCTGCTGCTGCTGCTGCT	p.Gly221AlafsTer74	frameshift_variant	Exon 5 of 6		NP_001276081.1
MICA	NM_001289153.2	c.661_662insCTGCTGCTGCTGCTGCT	p.Gly221AlafsTer74	frameshift_variant	Exon 5 of 6		NP_001276082.1
MICA	NM_001289154.2	c.538_539insCTGCTGCTGCTGCTGCT	p.Gly180AlafsTer74	frameshift_variant	Exon 5 of 6		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.952_953insCTGCTGCTGCTGCTGCT	p.Gly318AlafsTer74	frameshift_variant	Exon 5 of 6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 9.27e-7 AC: 1 AN: 1078846 Hom.: 0 Cov.: 35 AF XY: 0.00000187 AC XY: 1 AN XY: 534690

African (AFR) AF: 0.00 AC: 0 AN: 30192

American (AMR) AF: 0.00 AC: 0 AN: 30014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21796

East Asian (EAS) AF: 0.00 AC: 0 AN: 23478

South Asian (SAS) AF: 0.00 AC: 0 AN: 65974

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4828

European-Non Finnish (NFE) AF: 0.00000121 AC: 1 AN: 823124

Other (OTH) AF: 0.00 AC: 0 AN: 45676

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.64
Mutation Taster		=182/18	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;