Genetic Variant NM_138272.3:c.312C>A (chr6-31723889-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

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

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0380

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 Benign. Variant got -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 id is 3055478.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-31723889-C-A is described in Lovd as [Likely_benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPIG6B	NM_138272.3 link	c.312C>A	p.Gly104Gly	synonymous_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.312C>A	p.Gly104Gly	synonymous_variant	Exon 2 of 6		NM_138272.3	ENSP00000497720.1		O95866-1

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4076

AN:

152166

Hom.:

157

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00997

AC:

2389

AN:

239602

Hom.:

AF XY:

0.00820

AC XY:

1071

AN XY:

130540

show subpopulations

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 SAS 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.:

AF XY:

0.00413

AC XY:

2988

AN XY:

723808

show subpopulations

Gnomad4 AFR exome

AF:

0.0875

Gnomad4 AMR exome

AF:

0.0208

Gnomad4 ASJ exome

AF:

0.000896

Gnomad4 EAS exome

AF:

0.00686

Gnomad4 SAS exome

AF:

0.00167

Gnomad4 FIN exome

AF:

0.000264

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00962

GnomAD4 genome

AF:

0.0268

AC:

4077

AN:

152284

Hom.:

156

Cov.:

AF XY:

0.0263

AC XY:

1960

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0845

Gnomad4 AMR

AF:

0.0190

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00347

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00235

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.00984

Hom.:

Bravo

AF:

0.0308

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MPIG6B-related disorder

Benign:1

Dec 23, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

8.8

DANN

Benign

0.90

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over