6-31412384-G-GCTGCT

Variant names:

• chr6-31412384-G-GCTGCT
• rs41293539
• NM_001177519.3:c.952_953insCTGCT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001177519.3(MICA):​c.952_953insCTGCT​(p.Gly318AlafsTer70) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,199,762 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.000017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000015 (1 hom.)
• Consequence: MICA NM_001177519.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.952_953insCTGCT	p.Gly318AlafsTer70	frameshift_variant	Exon 5 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.661_662insCTGCT	p.Gly221AlafsTer70	frameshift_variant	Exon 5 of 6		NP_001276081.1
MICA	NM_001289153.2	c.661_662insCTGCT	p.Gly221AlafsTer70	frameshift_variant	Exon 5 of 6		NP_001276082.1
MICA	NM_001289154.2	c.538_539insCTGCT	p.Gly180AlafsTer70	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_953insCTGCT	p.Gly318AlafsTer70	frameshift_variant	Exon 5 of 6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.00000827 AC: 1 AN: 120862 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000264

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000148 AC: 16 AN: 1078816 Hom.: 1 Cov.: 35 AF XY: 0.0000131 AC XY: 7 AN XY: 534672

Gnomad4 AFR exome AF: 0.0000663

Gnomad4 AMR exome AF: 0.000133

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000852

Gnomad4 SAS exome AF: 0.0000303

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000729

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000165 AC: 2 AN: 120946 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 58766

Gnomad4 AFR AF: 0.0000527

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41293539; hg19: chr6-31380161;