6-31506266-C-T

Position:

chr6-31506266-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005931.5(MICB):c.449C>T(p.Ser150Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,614,060 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

MICB
NM_005931.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.836

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:

MICB (HGNC:):

MICB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042699754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MICB	NM_005931.5 linkuse as main transcript	c.449C>T	p.Ser150Leu	missense_variant	3/6	ENST00000252229.7	NP_005922.2	Q29980-1A0A7D9H7X8
MICB	NM_001289160.2 linkuse as main transcript	c.353C>T	p.Ser118Leu	missense_variant	3/6		NP_001276089.1	Q29980F5H7Q8B7Z8M1B4DUT9
MICB	NM_001289161.2 linkuse as main transcript	c.326-6C>T		splice_region_variant, intron_variant			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.449C>T	p.Ser150Leu	missense_variant	3/6	1	NM_005931.5	ENSP00000252229.6	Q29980-1
MICB	ENST00000399150.7 linkuse as main transcript	c.326-6C>T		splice_region_variant, intron_variant		1		ENSP00000382103.3	Q29980-2
MICB	ENST00000538442.5 linkuse as main transcript	c.353C>T	p.Ser118Leu	missense_variant	3/6	2		ENSP00000442345.1	F5H7Q8
MICB	ENST00000494577.1 linkuse as main transcript	n.332C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000124

AC:

AN:

249556

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000256

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000317

AC:

463

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

235

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000379

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000210

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000211

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000108

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

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

May 15, 2024

The c.449C>T (p.S150L) alteration is located in exon 3 (coding exon 3) of the MICB gene. This alteration results from a C to T substitution at nucleotide position 449, causing the serine (S) at amino acid position 150 to be replaced by a leucine (L). 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

0.086

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.6

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.012

M_CAP

Benign

0.0048

MetaRNN

Benign

0.043

T;T

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.27

PROVEAN

Benign

0.37

N;N

REVEL

Benign

0.059

Sift

Benign

0.038

D;D

Sift4G

Benign

0.27

T;T

Polyphen

0.0020

B;.

Vest4

0.13

MVP

0.19

MPC

0.22

ClinPred

0.044

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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