chr6-31412154-G-C

Variant names:

• chr6-31412154-G-C
• rs1063635
• NM_001177519.3:c.821G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001177519.3(MICA):​c.821G>C​(p.Arg274Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R274Q) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: MICA NM_001177519.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 54 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1175524).

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.821G>C	p.Arg274Pro	missense	Exon 4 of 6	NP_001170990.1	Q96QC4
	MICA	NM_001289152.2		c.530G>C	p.Arg177Pro	missense	Exon 4 of 6	NP_001276081.1	A0A024RCL3
	MICA	NM_001289153.2		c.530G>C	p.Arg177Pro	missense	Exon 4 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.821G>C	p.Arg274Pro	missense	Exon 4 of 6	ENSP00000413079.1	Q96QC4
	MICA	ENST00000892120.1		c.566G>C	p.Arg189Pro	missense	Exon 3 of 5	ENSP00000562179.1
	MICA	ENST00000616296.4	TSL:5	c.530G>C	p.Arg177Pro	missense	Exon 4 of 6	ENSP00000482382.1	A0A024RCL3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 79

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.95
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0039	N
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
PhyloP100		0.0040
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.087
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.33	T
Polyphen		0.82	P
Vest4		0.11
MutPred		0.55		Loss of MoRF binding (P = 0.0683)
MVP		0.040
MPC		0.39
ClinPred		0.31	T
GERP RS		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.51
Mutation Taster		=99/1	polymorphism

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: rs1063635; hg19: chr6-31379931;