chr6-31718720-G-A

Variant names:

• chr6-31718720-G-A
• rs15574
• NM_025261.3:c.*376C>T

Variant summary

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

The NM_025261.3(LY6G6C):​c.*376C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 291,228 control chromosomes in the GnomAD database, including 13,210 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 0.32 (8723 hom., cov: 30)
  • Exomes 𝑓: 0.24 (4487 hom.)
• Consequence: LY6G6C NM_025261.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 29 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6G6C	NM_025261.3	c.*376C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000375819.3	NP_079537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G6C	ENST00000375819.3	c.*376C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_025261.3	ENSP00000364978.2
LY6G6C	ENST00000495859.1	c.*376C>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000433207.1
MPIG6B	ENST00000460663.5	n.90+37G>A		intron_variant	Intron 1 of 6	3

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48461 AN: 151686 Hom.: 8704 Cov.: 30

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.236 AC: 32899 AN: 139424 Hom.: 4487 Cov.: 0 AF XY: 0.233 AC XY: 16257 AN XY: 69910

African (AFR) AF: 0.443 AC: 2218 AN: 5010

American (AMR) AF: 0.310 AC: 1919 AN: 6190

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1420 AN: 5676

East Asian (EAS) AF: 0.296 AC: 3784 AN: 12784

South Asian (SAS) AF: 0.221 AC: 666 AN: 3008

European-Finnish (FIN) AF: 0.363 AC: 2848 AN: 7856

Middle Eastern (MID) AF: 0.221 AC: 162 AN: 734

European-Non Finnish (NFE) AF: 0.198 AC: 17559 AN: 88548

Other (OTH) AF: 0.242 AC: 2323 AN: 9618

GnomAD4 genome AF: 0.320 AC: 48533 AN: 151804 Hom.: 8723 Cov.: 30 AF XY: 0.326 AC XY: 24223 AN XY: 74194

African (AFR) AF: 0.479 AC: 19786 AN: 41346

American (AMR) AF: 0.340 AC: 5188 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 896 AN: 3458

East Asian (EAS) AF: 0.241 AC: 1244 AN: 5172

South Asian (SAS) AF: 0.290 AC: 1392 AN: 4800

European-Finnish (FIN) AF: 0.396 AC: 4161 AN: 10518

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14923 AN: 67924

Other (OTH) AF: 0.319 AC: 674 AN: 2112

Alfa AF: 0.248 Hom.: 16605

Bravo AF: 0.324

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.62
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs15574; hg19: chr6-31686497;