Genetic Variant MPIG6B:p.Pro62Leu (chr6-31723762-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138272.3(MPIG6B):c.185C>T(p.Pro62Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P62Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

MPIG6B
NM_138272.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.35087278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPIG6B	NM_138272.3 link	c.185C>T	p.Pro62Leu	missense_variant	Exon 2 of 6	ENST00000649779.1	NP_612116.1	O95866-1B0V023

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPIG6B	ENST00000649779.1 link	c.185C>T	p.Pro62Leu	missense_variant	Exon 2 of 6		NM_138272.3	ENSP00000497720.1		O95866-1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

249892

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135386

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000575

AC:

AN:

1461550

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000638

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000978

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;.;.;.;T;.;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.93

D;D;D;D;.;D;D;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.35

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

.;M;M;M;M;M;M;M

PROVEAN

Pathogenic

-8.5

D;D;D;D;.;D;D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D;D;D;.;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;.;D;D;D

Polyphen

0.99, 0.94, 0.96, 0.99

.;D;P;.;D;D;D;D

Vest4

0.51

MutPred

0.52

Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);Loss of disorder (P = 0.018);

MVP

0.49

MPC

0.96

ClinPred

0.46

GERP RS

3.0

Varity_R

0.17

gMVP

0.82

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over