6-31505823-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005931.5(MICB):c.277G>A(p.Gly93Arg) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MICB NM_005931.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0760

Genes affected

MICB (HGNC:7091): (MHC class I polypeptide-related sequence B) This gene encodes a heavily glycosylated protein which is a ligand for the NKG2D type II receptor. Binding of the ligand activates the cytolytic response of natural killer (NK) cells, CD8 alphabeta T cells, and gammadelta T cells which express the receptor. This protein is stress-induced and is similar to MHC class I molecules; however, it does not associate with beta-2-microglobulin or bind peptides. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12850615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MICB	NM_005931.5	c.277G>A	p.Gly93Arg	missense_variant	2/6	ENST00000252229.7
MICB	NM_001289160.2	c.181G>A	p.Gly61Arg	missense_variant	2/6
MICB	NM_001289161.2	c.277G>A	p.Gly93Arg	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MICB	ENST00000252229.7	c.277G>A	p.Gly93Arg	missense_variant	2/6	1	NM_005931.5	P1
MICB	ENST00000399150.7	c.277G>A	p.Gly93Arg	missense_variant	2/6	1
MICB	ENST00000538442.5	c.181G>A	p.Gly61Arg	missense_variant	2/6	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.277G>A (p.G93R) alteration is located in exon 2 (coding exon 2) of the MICB gene. This alteration results from a G to A substitution at nucleotide position 277, causing the glycine (G) at amino acid position 93 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	2.0
Dann	Uncertain	0.98
DEOGEN2	Benign	0.010	T;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0064	N
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.12	T;D;T
Sift4G	Benign	0.63	T;T;T
Polyphen		1.0	D;.;.
Vest4		0.15
MutPred		0.40		.;Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);
MVP		0.44
MPC		0.99
ClinPred		0.20	T
GERP RS		0.098
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31473600;