6-31506223-G-C

Variant names:

• chr6-31506223-G-C
• rs1051788
• NM_005931.5:c.406G>C

Variant summary

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

The NM_005931.5(MICB):​c.406G>C​(p.Asp136His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MICB NM_005931.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.615
• Publications: 42 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005931.5. 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
	MICB	NM_005931.5	MANE Select	c.406G>C	p.Asp136His	missense	Exon 3 of 6	NP_005922.2	A0A7D9H7X8
	MICB	NM_001289160.2		c.310G>C	p.Asp104His	missense	Exon 3 of 6	NP_001276089.1	F5H7Q8
	MICB	NM_001289161.2		c.326-49G>C		intron	N/A	NP_001276090.1	Q29980-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MICB	ENST00000252229.7	TSL:1 MANE Select	c.406G>C	p.Asp136His	missense	Exon 3 of 6	ENSP00000252229.6	Q29980-1
	MICB	ENST00000399150.7	TSL:1	c.326-49G>C		intron	N/A	ENSP00000382103.3	Q29980-2
	MICB	ENST00000538442.5	TSL:2	c.310G>C	p.Asp104His	missense	Exon 3 of 6	ENSP00000442345.1	F5H7Q8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.060	N
M_CAP	Benign	0.0050	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Benign	0.069
Sift	Benign	0.030	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.75		Gain of sheet (P = 0.0827)
MVP		0.34
MPC		0.97
ClinPred		0.76	D
GERP RS		-0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.68
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1051788; hg19: chr6-31474000;