Variant chr6-31720152-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025261.3(LY6G6C):c.104A>C(p.Asp35Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LY6G6C
NM_025261.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6G6C	NM_025261.3 linkuse as main transcript	c.104A>C	p.Asp35Ala	missense_variant	2/3	ENST00000375819.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LY6G6C	ENST00000375819.3 linkuse as main transcript	c.104A>C	p.Asp35Ala	missense_variant	2/3	1	NM_025261.3	P1
LY6G6C	ENST00000495859.1 linkuse as main transcript	c.-65A>C		5_prime_UTR_variant	3/4	1
MPIG6B	ENST00000460663.5 linkuse as main transcript	n.90+1469T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246754

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134404

show subpopulations

Gnomad AFR exome

AF:

0.0000660

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460774

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726704

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000869

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 20, 2023

The c.104A>C (p.D35A) alteration is located in exon 2 (coding exon 2) of the LY6G6C gene. This alteration results from a A to C substitution at nucleotide position 104, causing the aspartic acid (D) at amino acid position 35 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.82

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.039

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Benign

0.70

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.97

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.54

Sift

Uncertain

0.016

Sift4G

Uncertain

0.020

Polyphen

0.83

Vest4

0.54

MutPred

0.46

Gain of sheet (P = 0.0827);

MVP

0.64

MPC

0.82

ClinPred

0.61

GERP RS

5.1

Varity_R

0.20

gMVP

0.66

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