6-31723731-G-T

Variant names:

• chr6-31723731-G-T
• rs141914091
• NM_138272.3:c.154G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138272.3(MPIG6B):​c.154G>T​(p.Ala52Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A52T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: MPIG6B NM_138272.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.715
• Publications: 0 publications found

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]

MPIG6B Gene-Disease associations (from GenCC):

• thrombocytopenia, anemia, and myelofibrosis

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2914921).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138272.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPIG6B	NM_138272.3	MANE Select	c.154G>T	p.Ala52Ser	missense	Exon 2 of 6	NP_612116.1	O95866-1
	MPIG6B	NM_025260.4		c.154G>T	p.Ala52Ser	missense	Exon 2 of 6	NP_079536.2
	MPIG6B	NM_138277.3		c.154G>T	p.Ala52Ser	missense	Exon 2 of 5	NP_612121.1	O95866-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPIG6B	ENST00000649779.1	MANE Select	c.154G>T	p.Ala52Ser	missense	Exon 2 of 6	ENSP00000497720.1	O95866-1
	MPIG6B	ENST00000375809.7	TSL:1	c.154G>T	p.Ala52Ser	missense	Exon 2 of 6	ENSP00000364967.3	O95866-2
	MPIG6B	ENST00000375810.8	TSL:1	c.154G>T	p.Ala52Ser	missense	Exon 2 of 5	ENSP00000364968.4	O95866-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460918 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726822

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52674

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111896

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.091	T
Eigen	Benign	0.0088
Eigen_PC	Benign	-0.090
FATHMM_MKL	Benign	0.19	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.71
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.93	P
Vest4		0.41
MutPred		0.53		Gain of relative solvent accessibility (P = 0.0082)
MVP		0.53
MPC		0.80
ClinPred		0.92	D
GERP RS		4.8
PromoterAI		-0.034	Neutral
Varity_R		0.23
gMVP		0.55
Mutation Taster		=85/15	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs141914091; hg19: chr6-31691508; COSMIC: COSV101008019; COSMIC: COSV101008019;