6-31723900-G-T

Position:

• chr6-31723900-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138272.3(MPIG6B):​c.323G>T​(p.Cys108Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPIG6B NM_138272.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

Genes affected

MPIG6B (HGNC:13937): (megakaryocyte and platelet inhibitory receptor G6b) This gene is a member of the immunoglobulin (Ig) superfamily and is located in the major histocompatibility complex (MHC) class III region. The protein encoded by this gene is a glycosylated, plasma membrane-bound cell surface receptor, but soluble isoforms encoded by some transcript variants have been found in the endoplasmic reticulum and Golgi before being secreted. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.778

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPIG6B	NM_138272.3	c.323G>T	p.Cys108Phe	missense_variant	2/6	ENST00000649779.1	NP_612116.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPIG6B	ENST00000649779.1	c.323G>T	p.Cys108Phe	missense_variant	2/6		NM_138272.3	ENSP00000497720	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Thrombocytopenia, anemia, and myelofibrosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

3billion

May 22, 2022

The variant is not observed in the gnomAD v2.1.1 dataset. Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.44; 3Cnet: 0.80). Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.;.;T;.;.;T
Eigen	Benign	0.048
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.89	D;D;D;D;.;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.78	D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.3	.;M;M;M;M;M;M;M
MutationTaster	Benign	0.99	D;D;D;D;D;D;D
PROVEAN	Pathogenic	-11	D;D;D;D;.;D;D;D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D;D;D;D;.;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;.;D;D;D
Polyphen		0.39, 0.99, 0.090, 0.56	.;B;D;.;B;P;B;B
Vest4		0.79
MutPred		0.66		Gain of catalytic residue at C108 (P = 0.0747);Gain of catalytic residue at C108 (P = 0.0747);Gain of catalytic residue at C108 (P = 0.0747);Gain of catalytic residue at C108 (P = 0.0747);Gain of catalytic residue at C108 (P = 0.0747);Gain of catalytic residue at C108 (P = 0.0747);Gain of catalytic residue at C108 (P = 0.0747);Gain of catalytic residue at C108 (P = 0.0747);
MVP		0.53
MPC		1.5
ClinPred		1.0	D
GERP RS		4.1
Varity_R		0.53
gMVP		1.0

Splicing

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: chr6-31691677;