Variant chr6-31505685-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005931.5(MICB):c.139G>A(p.Ala47Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MICB
NM_005931.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.688

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.09425259).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICB	NM_005931.5 linkuse as main transcript	c.139G>A	p.Ala47Thr	missense_variant	2/6	ENST00000252229.7	NP_005922.2	Q29980-1A0A7D9H7X8
MICB	NM_001289160.2 linkuse as main transcript	c.43G>A	p.Ala15Thr	missense_variant	2/6		NP_001276089.1	Q29980F5H7Q8B7Z8M1B4DUT9
MICB	NM_001289161.2 linkuse as main transcript	c.139G>A	p.Ala47Thr	missense_variant	2/6		NP_001276090.1	Q29980-2A0A0G2JHB5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MICB	ENST00000252229.7 linkuse as main transcript	c.139G>A	p.Ala47Thr	missense_variant	2/6	1	NM_005931.5	ENSP00000252229.6	Q29980-1
MICB	ENST00000399150.7 linkuse as main transcript	c.139G>A	p.Ala47Thr	missense_variant	2/6	1		ENSP00000382103.3	Q29980-2
MICB	ENST00000538442.5 linkuse as main transcript	c.43G>A	p.Ala15Thr	missense_variant	2/6	2		ENSP00000442345.1	F5H7Q8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

244714

Hom.:

AF XY:

0.0000523

AC XY:

AN XY:

133910

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000544

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1460694

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

726662

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000335

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2023

The c.139G>A (p.A47T) 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 139, causing the alanine (A) at amino acid position 47 to be replaced by a threonine (T). 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

0.20

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.4

DANN

Benign

0.97

DEOGEN2

Benign

0.012

T;T;.

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.014

M_CAP

Benign

0.0074

MetaRNN

Benign

0.094

T;T;T

MetaSVM

Benign

-0.89

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-2.6

D;N;D

REVEL

Benign

0.025

Sift

Benign

0.063

T;T;T

Sift4G

Uncertain

0.049

D;T;T

Polyphen

0.17

B;.;.

Vest4

0.11

MutPred

0.64

.;Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.16

MPC

0.28

ClinPred

0.076

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.29

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over