chr6-31723889-C-A

Variant names:

• chr6-31723889-C-A
• rs4947252
• NM_138272.3:c.312C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_138272.3(MPIG6B):​c.312C>A​(p.Gly104Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00664 in 1,608,086 control chromosomes in the GnomAD database, including 325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.027 (156 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (169 hom.)
• Consequence: MPIG6B NM_138272.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.0380
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 6-31723889-C-A is Benign according to our data. Variant chr6-31723889-C-A is described in ClinVar as Benign. ClinVar VariationId is 3055478.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.038 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0822 is higher than 0.05.

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.312C>A	p.Gly104Gly	synonymous	Exon 2 of 6	NP_612116.1	O95866-1
	MPIG6B	NM_025260.4		c.312C>A	p.Gly104Gly	synonymous	Exon 2 of 6	NP_079536.2
	MPIG6B	NM_138277.3		c.312C>A	p.Gly104Gly	synonymous	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.312C>A	p.Gly104Gly	synonymous	Exon 2 of 6	ENSP00000497720.1	O95866-1
	MPIG6B	ENST00000375809.7	TSL:1	c.312C>A	p.Gly104Gly	synonymous	Exon 2 of 6	ENSP00000364967.3	O95866-2
	MPIG6B	ENST00000375810.8	TSL:1	c.312C>A	p.Gly104Gly	synonymous	Exon 2 of 5	ENSP00000364968.4	O95866-7

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4076 AN: 152166 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.00538

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00235

Gnomad OTH AF: 0.0258

GnomAD2 exomes AF: 0.00997 AC: 2389 AN: 239602 AF XY: 0.00820

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.0211

Gnomad ASJ exome AF: 0.000749

Gnomad EAS exome AF: 0.00161

Gnomad FIN exome AF: 0.0000470

Gnomad NFE exome AF: 0.00264

Gnomad OTH exome AF: 0.00587

GnomAD4 exome AF: 0.00453 AC: 6596 AN: 1455802 Hom.: 169 Cov.: 34 AF XY: 0.00413 AC XY: 2988 AN XY: 723808

African (AFR) AF: 0.0875 AC: 2907 AN: 33238

American (AMR) AF: 0.0208 AC: 912 AN: 43778

Ashkenazi Jewish (ASJ) AF: 0.000896 AC: 23 AN: 25678

East Asian (EAS) AF: 0.00686 AC: 272 AN: 39638

South Asian (SAS) AF: 0.00167 AC: 143 AN: 85632

European-Finnish (FIN) AF: 0.000264 AC: 14 AN: 53074

Middle Eastern (MID) AF: 0.0141 AC: 81 AN: 5740

European-Non Finnish (NFE) AF: 0.00150 AC: 1666 AN: 1108932

Other (OTH) AF: 0.00962 AC: 578 AN: 60092

GnomAD4 genome AF: 0.0268 AC: 4077 AN: 152284 Hom.: 156 Cov.: 32 AF XY: 0.0263 AC XY: 1960 AN XY: 74468

African (AFR) AF: 0.0845 AC: 3511 AN: 41546

American (AMR) AF: 0.0190 AC: 291 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5184

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4826

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10624

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00235 AC: 160 AN: 68014

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

Alfa AF: 0.0110 Hom.: 68

Bravo AF: 0.0308

Asia WGS AF: 0.00549 AC: 20 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MPIG6B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.8
DANN	Benign	0.90
PhyloP100		0.038
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4947252; hg19: chr6-31691666;