rs805293

Variant names:

• chr6-31720741-T-A
• rs805293
• NM_025261.3:c.53-538A>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31720741-T-A
• chr6-31720741-T-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.53-538A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,988 control chromosomes in the GnomAD database, including 12,897 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 0.40 (12897 hom., cov: 31)
• Consequence: LY6G6C NM_025261.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17
• Publications: 30 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G6C	NM_025261.3	c.53-538A>T		intron_variant	Intron 1 of 2	ENST00000375819.3	NP_079537.1
MPIG6B	XM_017011333.2	c.-93T>A		5_prime_UTR_variant	Exon 1 of 4		XP_016866822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G6C	ENST00000375819.3	c.53-538A>T		intron_variant	Intron 1 of 2	1	NM_025261.3	ENSP00000364978.2
LY6G6C	ENST00000495859.1	c.-117+212A>T		intron_variant	Intron 2 of 3	1		ENSP00000433207.1
MPIG6B	ENST00000460663.5	n.90+2058T>A		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60815 AN: 151870 Hom.: 12888 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.400 AC: 60848 AN: 151988 Hom.: 12897 Cov.: 31 AF XY: 0.398 AC XY: 29608 AN XY: 74300

African (AFR) AF: 0.260 AC: 10784 AN: 41470

American (AMR) AF: 0.468 AC: 7137 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1993 AN: 3470

East Asian (EAS) AF: 0.391 AC: 2021 AN: 5172

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4814

European-Finnish (FIN) AF: 0.364 AC: 3839 AN: 10554

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.462 AC: 31417 AN: 67930

Other (OTH) AF: 0.423 AC: 892 AN: 2108

Alfa AF: 0.422 Hom.: 1836

Bravo AF: 0.402

Asia WGS AF: 0.377 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.78
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs805293; hg19: chr6-31688518;