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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MICB	NM_005931.5	c.406G>C	p.Asp136His	missense_variant	Exon 3 of 6	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.310G>C	p.Asp104His	missense_variant	Exon 3 of 6		NP_001276089.1
MICB	NM_001289161.2	c.326-49G>C		intron_variant	Intron 2 of 5		NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.406G>C	p.Asp136His	missense_variant	Exon 3 of 6	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.326-49G>C		intron_variant	Intron 2 of 5	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.310G>C	p.Asp104His	missense_variant	Exon 3 of 6	2		ENSP00000442345.1
MICB	ENST00000494577.1	n.289G>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 56

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.61
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Benign	0.069
Sift	Benign	0.030	D;D
Sift4G	Uncertain	0.0090	D;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;