6-31720440-A-G

Variant names:

• chr6-31720440-A-G
• rs805294
• NM_025261.3:c.53-237T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025261.3(LY6G6C):​c.53-237T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,054 control chromosomes in the GnomAD database, including 18,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18799 hom., cov: 32)
• Consequence: LY6G6C NM_025261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0620
• Publications: 45 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025261.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY6G6C	NM_025261.3	MANE Select	c.53-237T>C		intron	N/A	NP_079537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY6G6C	ENST00000375819.3	TSL:1 MANE Select	c.53-237T>C		intron	N/A	ENSP00000364978.2
	LY6G6C	ENST00000495859.1	TSL:1	c.-116-237T>C		intron	N/A	ENSP00000433207.1
	MPIG6B	ENST00000460663.5	TSL:3	n.90+1757A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72155 AN: 151936 Hom.: 18764 Cov.: 32

Gnomad AFR AF: 0.706

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.473

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.475 AC: 72240 AN: 152054 Hom.: 18799 Cov.: 32 AF XY: 0.477 AC XY: 35473 AN XY: 74310

African (AFR) AF: 0.706 AC: 29249 AN: 41442

American (AMR) AF: 0.442 AC: 6758 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1215 AN: 3470

East Asian (EAS) AF: 0.395 AC: 2041 AN: 5170

South Asian (SAS) AF: 0.443 AC: 2132 AN: 4818

European-Finnish (FIN) AF: 0.480 AC: 5088 AN: 10590

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24367 AN: 67962

Other (OTH) AF: 0.476 AC: 1006 AN: 2114

Alfa AF: 0.392 Hom.: 52028

Bravo AF: 0.483

Asia WGS AF: 0.516 AC: 1791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.8
DANN	Benign	0.53
PhyloP100		-0.062
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs805294; hg19: chr6-31688217;