Genetic Variant NM_001177519.3:c.952_953insCTGCTGCTGCTGCTGCTGCT (chr6-31412384-G-GCTGCTGCTGCTGCTGCTGCT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001177519.3(MICA):c.952_953insCTGCTGCTGCTGCTGCTGCT(p.Gly318AlafsTer75) 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 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MICA
NM_001177519.3 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.641

Publications

18 publications found

Variant links:

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]

MICA links:

ENSG00000288587 (HGNC:):

ENSG00000288587 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 link	c.952_953insCTGCTGCTGCTGCTGCTGCT	p.Gly318AlafsTer75	frameshift_variant	Exon 5 of 6	ENST00000449934.7	NP_001170990.1	Q96QC4
MICA	NM_001289152.2 link	c.661_662insCTGCTGCTGCTGCTGCTGCT	p.Gly221AlafsTer75	frameshift_variant	Exon 5 of 6		NP_001276081.1	Q96QC4A0A024RCL3
MICA	NM_001289153.2 link	c.661_662insCTGCTGCTGCTGCTGCTGCT	p.Gly221AlafsTer75	frameshift_variant	Exon 5 of 6		NP_001276082.1	Q96QC4A0A024RCL3
MICA	NM_001289154.2 link	c.538_539insCTGCTGCTGCTGCTGCTGCT	p.Gly180AlafsTer75	frameshift_variant	Exon 5 of 6		NP_001276083.1	Q96QC4A0A0G2JJ55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7 link	c.952_953insCTGCTGCTGCTGCTGCTGCT	p.Gly318AlafsTer75	frameshift_variant	Exon 5 of 6	1	NM_001177519.3	ENSP00000413079.1		Q96QC4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

120862

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000371

AC:

AN:

1078846

Hom.:

Cov.:

AF XY:

0.00000187

AC XY:

AN XY:

534690

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000331

AC:

AN:

30192

American (AMR)

AF:

0.00

AC:

AN:

30014

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21796

East Asian (EAS)

AF:

0.00

AC:

AN:

23478

South Asian (SAS)

AF:

0.00

AC:

AN:

65974

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4828

European-Non Finnish (NFE)

AF:

0.00000364

AC:

AN:

823124

Other (OTH)

AF:

0.00

AC:

AN:

45676

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00383038), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

120862

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

58666

African (AFR)

AF:

0.00

AC:

AN:

37864

American (AMR)

AF:

0.00

AC:

AN:

12414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3034

East Asian (EAS)

AF:

0.00

AC:

AN:

2846

South Asian (SAS)

AF:

0.00

AC:

AN:

3830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7206

Middle Eastern (MID)

AF:

0.00

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

50914

Other (OTH)

AF:

0.00

AC:

AN:

1718

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.64

Mutation Taster

=182/18

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over