chr6-31723762-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_138272.3(MPIG6B):c.185C>A(p.Pro62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,613,876 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

MPIG6B
NM_138272.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0330

Publications

4 publications found

Variant links:

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

MPIG6B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0106242895).

BP6

Variant 6-31723762-C-A is Benign according to our data. Variant chr6-31723762-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3057590.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00134 (204/152324) while in subpopulation AFR AF = 0.00469 (195/41578). AF 95% confidence interval is 0.00415. There are 1 homozygotes in GnomAd4. There are 104 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPIG6B	NM_138272.3	MANE Select	c.185C>A	p.Pro62Gln	missense	Exon 2 of 6	NP_612116.1	O95866-1
MPIG6B	NM_025260.4		c.185C>A	p.Pro62Gln	missense	Exon 2 of 6	NP_079536.2
MPIG6B	NM_138277.3		c.185C>A	p.Pro62Gln	missense	Exon 2 of 5	NP_612121.1	O95866-7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPIG6B	ENST00000649779.1	MANE Select	c.185C>A	p.Pro62Gln	missense	Exon 2 of 6	ENSP00000497720.1	O95866-1
MPIG6B	ENST00000375809.7	TSL:1	c.185C>A	p.Pro62Gln	missense	Exon 2 of 6	ENSP00000364967.3	O95866-2
MPIG6B	ENST00000375810.8	TSL:1	c.185C>A	p.Pro62Gln	missense	Exon 2 of 5	ENSP00000364968.4	O95866-7

Frequencies

GnomAD3 genomes

AF:

0.00134

AC:

204

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00470

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000356

AC:

AN:

249892

AF XY:

0.000295

show subpopulations

Gnomad AFR exome

AF:

0.00487

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000155

AC:

227

AN:

1461552

Hom.:

Cov.:

AF XY:

0.000128

AC XY:

AN XY:

727100

show subpopulations

African (AFR)

AF:

0.00588

AC:

197

AN:

33480

American (AMR)

AF:

0.000268

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53114

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1112002

Other (OTH)

AF:

0.000132

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00134

AC:

204

AN:

152324

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00469

AC:

195

AN:

41578

American (AMR)

AF:

0.000458

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000222

Hom.:

Bravo

AF:

0.00184

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MPIG6B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.085

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.077

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.049

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.2

PhyloP100

0.033

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.98

Vest4

0.35

MVP

0.43

MPC

1.0

ClinPred

0.12

GERP RS

3.0

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.17

gMVP

0.84

Mutation Taster

=93/7

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over