6-31723908-CG-C

Variant names:

• chr6-31723908-CG-C
• NM_138272.3:c.332delG

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_138272.3(MPIG6B):​c.332delG​(p.Arg111ProfsTer34) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPIG6B NM_138272.3 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.127
• 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-31723908-CG-C is Pathogenic according to our data. Variant chr6-31723908-CG-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 2627094.Status of the report is no_assertion_criteria_provided, 0 stars.

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.332delG	p.Arg111ProfsTer34	frameshift	Exon 2 of 6	NP_612116.1	O95866-1
	MPIG6B	NM_025260.4		c.332delG	p.Arg111ProfsTer34	frameshift	Exon 2 of 6	NP_079536.2
	MPIG6B	NM_138277.3		c.332delG	p.Arg111ProfsTer34	frameshift	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.332delG	p.Arg111ProfsTer34	frameshift	Exon 2 of 6	ENSP00000497720.1	O95866-1
	MPIG6B	ENST00000375809.7	TSL:1	c.332delG	p.Arg111ProfsTer34	frameshift	Exon 2 of 6	ENSP00000364967.3	O95866-2
	MPIG6B	ENST00000375810.8	TSL:1	c.332delG	p.Arg111ProfsTer34	frameshift	Exon 2 of 5	ENSP00000364968.4	O95866-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Thrombocytopenia, anemia, and myelofibrosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

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

Other links and lift over

hg19: chr6-31691685;