NM_001177519.3:c.433C>G

Variant names:

• chr6-31411179-C-G
• rs1051790
• NM_001177519.3:c.433C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177519.3(MICA):​c.433C>G​(p.Leu145Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,612,840 control chromosomes in the GnomAD database, including 25,341 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (3169 hom., cov: 31)
  • Exomes 𝑓: 0.16 (22172 hom.)
• Consequence: MICA NM_001177519.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.826
• Publications: 26 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0060625076).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICA	NM_001177519.3	c.433C>G	p.Leu145Val	missense_variant	Exon 3 of 6	ENST00000449934.7	NP_001170990.1
MICA	NM_001289152.2	c.142C>G	p.Leu48Val	missense_variant	Exon 3 of 6		NP_001276081.1
MICA	NM_001289153.2	c.142C>G	p.Leu48Val	missense_variant	Exon 3 of 6		NP_001276082.1
MICA	NM_001289154.2	c.84-65C>G		intron_variant	Intron 2 of 5		NP_001276083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICA	ENST00000449934.7	c.433C>G	p.Leu145Val	missense_variant	Exon 3 of 6	1	NM_001177519.3	ENSP00000413079.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28119 AN: 151688 Hom.: 3161 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.0779

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.171 AC: 42488 AN: 248204 AF XY: 0.179

Gnomad AFR exome AF: 0.246

Gnomad AMR exome AF: 0.162

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.0959

Gnomad FIN exome AF: 0.0785

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.161 AC: 235891 AN: 1461034 Hom.: 22172 Cov.: 61 AF XY: 0.166 AC XY: 120488 AN XY: 726804

African (AFR) AF: 0.254 AC: 8500 AN: 33442

American (AMR) AF: 0.175 AC: 7753 AN: 44312

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 5643 AN: 26128

East Asian (EAS) AF: 0.202 AC: 8021 AN: 39646

South Asian (SAS) AF: 0.276 AC: 23796 AN: 86162

European-Finnish (FIN) AF: 0.0805 AC: 4299 AN: 53406

Middle Eastern (MID) AF: 0.390 AC: 2248 AN: 5766

European-Non Finnish (NFE) AF: 0.149 AC: 165186 AN: 1111798

Other (OTH) AF: 0.173 AC: 10445 AN: 60374

GnomAD4 genome AF: 0.185 AC: 28146 AN: 151806 Hom.: 3169 Cov.: 31 AF XY: 0.185 AC XY: 13702 AN XY: 74234

African (AFR) AF: 0.244 AC: 10090 AN: 41268

American (AMR) AF: 0.216 AC: 3284 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3466

East Asian (EAS) AF: 0.120 AC: 618 AN: 5158

South Asian (SAS) AF: 0.277 AC: 1332 AN: 4814

European-Finnish (FIN) AF: 0.0779 AC: 826 AN: 10608

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10568 AN: 67974

Other (OTH) AF: 0.257 AC: 542 AN: 2106

Alfa AF: 0.138 Hom.: 572

Bravo AF: 0.200

TwinsUK AF: 0.136 AC: 504

ALSPAC AF: 0.150 AC: 580

ESP6500AA AF: 0.244 AC: 338

ESP6500EA AF: 0.154 AC: 489

ExAC AF: 0.174 AC: 21072

Asia WGS AF: 0.185 AC: 644 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.5
DANN	Benign	0.96
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.043	N
MetaRNN	Benign	0.0061	T;T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.83
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.85	.;N
REVEL	Benign	0.047
Sift	Benign	0.085	.;T
Sift4G	Benign	0.23	T;T
Polyphen		1.0	.;D
Vest4		0.078
MPC		0.53
ClinPred		0.010	T
GERP RS		1.9
gMVP		0.12
Mutation Taster		=94/6	polymorphism (auto)

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: rs1051790; hg19: chr6-31378956; COSMIC: COSV69826467;