chr6-31719250-G-C

Position:

chr6-31719250-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_025261.3(LY6G6C):c.224C>G(p.Ala75Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 1,614,198 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 120 hom. )

Consequence

LY6G6C
NM_025261.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.154

Variant links:

Genes affected

LY6G6C (HGNC:13936): (lymphocyte antigen 6 family member G6C) LY6G6C belongs to a cluster of leukocyte antigen-6 (LY6) genes located in the major histocompatibility complex (MHC) class III region on chromosome 6. Members of the LY6 superfamily typically contain 70 to 80 amino acids, including 8 to 10 cysteines. Most LY6 proteins are attached to the cell surface by a glycosylphosphatidylinositol (GPI) anchor that is directly involved in signal transduction (Mallya et al., 2002 [PubMed 12079290]).[supplied by OMIM, Mar 2008]

LY6G6C links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016444623).

BP6

Variant 6-31719250-G-C is Benign according to our data. Variant chr6-31719250-G-C is described in ClinVar as [Benign]. Clinvar id is 783628.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00568 (8298/1461878) while in subpopulation EAS AF= 0.0443 (1758/39700). AF 95% confidence interval is 0.0426. There are 120 homozygotes in gnomad4_exome. There are 4450 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6G6C	NM_025261.3 linkuse as main transcript	c.224C>G	p.Ala75Gly	missense_variant	3/3	ENST00000375819.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LY6G6C	ENST00000375819.3 linkuse as main transcript	c.224C>G	p.Ala75Gly	missense_variant	3/3	1	NM_025261.3	P1
LY6G6C	ENST00000495859.1 linkuse as main transcript	c.56C>G	p.Ala19Gly	missense_variant	4/4	1
MPIG6B	ENST00000460663.5 linkuse as main transcript	n.90+567G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00506

AC:

770

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00687

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0134

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00491

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00714

AC:

1795

AN:

251490

Hom.:

AF XY:

0.00801

AC XY:

1089

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00454

Gnomad ASJ exome

AF:

0.0377

Gnomad EAS exome

AF:

0.0130

Gnomad SAS exome

AF:

0.0122

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00493

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00568

AC:

8298

AN:

1461878

Hom.:

120

Cov.:

AF XY:

0.00612

AC XY:

4450

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000986

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.0398

Gnomad4 EAS exome

AF:

0.0443

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.000693

Gnomad4 NFE exome

AF:

0.00321

Gnomad4 OTH exome

AF:

0.00734

GnomAD4 genome

AF:

0.00506

AC:

770

AN:

152320

Hom.:

Cov.:

AF XY:

0.00553

AC XY:

412

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00686

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.0152

Gnomad4 SAS

AF:

0.0134

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00491

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00867

Hom.:

Bravo

AF:

0.00524

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00688

AC:

835

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00842

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.018

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-0.87

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.087

Sift

Benign

0.40

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0

.;B

Vest4

0.086

MVP

0.099

MPC

0.35

ClinPred

0.0015

GERP RS

0.84

Varity_R

0.033

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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