6-31505653-C-T

Position:

• chr6-31505653-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005931.5(MICB):​c.107C>T​(p.Ser36Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MICB NM_005931.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.132

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

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.107C>T	p.Ser36Phe	missense_variant	2/6	ENST00000252229.7	NP_005922.2
MICB	NM_001289160.2	c.11C>T	p.Ser4Phe	missense_variant	2/6		NP_001276089.1
MICB	NM_001289161.2	c.107C>T	p.Ser36Phe	missense_variant	2/6		NP_001276090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MICB	ENST00000252229.7	c.107C>T	p.Ser36Phe	missense_variant	2/6	1	NM_005931.5	ENSP00000252229.6
MICB	ENST00000399150.7	c.107C>T	p.Ser36Phe	missense_variant	2/6	1		ENSP00000382103.3
MICB	ENST00000538442.5	c.11C>T	p.Ser4Phe	missense_variant	2/6	2		ENSP00000442345.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

The c.107C>T (p.S36F) alteration is located in exon 2 (coding exon 2) of the MICB gene. This alteration results from a C to T substitution at nucleotide position 107, causing the serine (S) at amino acid position 36 to be replaced by a phenylalanine (F). 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	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.0093	N
M_CAP	Benign	0.0050	T
MetaRNN	Uncertain	0.59	D;D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.2	D;D;D
REVEL	Benign	0.084
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.15
MutPred		0.82		.;Loss of disorder (P = 0.0166);Loss of disorder (P = 0.0166);
MVP		0.51
MPC		0.95
ClinPred		0.98	D
GERP RS		0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-31473430;