6-31506223-G-C

Position:

• chr6-31506223-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D136N) has been classified as Likely benign.

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

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]

MICB (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

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

Ensembl

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051788; hg19: chr6-31474000;