rs11758242

chr6-31672068-C-Achr6-31672068-C-Gchr6-31672068-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021221.3(LY6G5B):c.392C>A(p.Ser131Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,613,012 control chromosomes in the GnomAD database, including 1,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.054 (407 hom., cov: 32)
  • Exomes 𝑓: 0.026 (1068 hom.)
• Consequence: LY6G5B NM_021221.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

Genes affected

LY6G5B (HGNC:13931): (lymphocyte antigen 6 family member G5B) LY6G5B 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017583966).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6G5B	NM_021221.3	c.392C>A	p.Ser131Tyr	missense_variant	3/3	ENST00000375864.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY6G5B	ENST00000375864.5	c.392C>A	p.Ser131Tyr	missense_variant	3/3	1	NM_021221.3	P1
LY6G5B	ENST00000409525.1	c.227C>A	p.Ser76Tyr	missense_variant	2/2	1

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8223 AN: 152084 Hom.: 402 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0186

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0800

GnomAD3 exomes AF: 0.0362 AC: 8925 AN: 246572 Hom.: 370 AF XY: 0.0328 AC XY: 4414 AN XY: 134386

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0564

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0134

Gnomad SAS exome AF: 0.0168

Gnomad FIN exome AF: 0.00268

Gnomad NFE exome AF: 0.0239

Gnomad OTH exome AF: 0.0506

GnomAD4 exome AF: 0.0261 AC: 38183 AN: 1460810 Hom.: 1068 Cov.: 31 AF XY: 0.0258 AC XY: 18766 AN XY: 726722

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0580

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.0449

Gnomad4 SAS exome AF: 0.0174

Gnomad4 FIN exome AF: 0.00283

Gnomad4 NFE exome AF: 0.0195

Gnomad4 OTH exome AF: 0.0404

GnomAD4 genome AF: 0.0542 AC: 8250 AN: 152202 Hom.: 407 Cov.: 32 AF XY: 0.0521 AC XY: 3880 AN XY: 74412

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0601

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0172

Gnomad4 SAS AF: 0.0182

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.0238

Gnomad4 OTH AF: 0.0791

Alfa AF: 0.0337 Hom.: 165

Bravo AF: 0.0623

TwinsUK AF: 0.0170 AC: 63

ALSPAC AF: 0.0187 AC: 72

ESP6500AA AF: 0.111 AC: 334

ESP6500EA AF: 0.0281 AC: 152

ExAC AF: 0.0343 AC: 4045

Asia WGS AF: 0.0310 AC: 107 AN: 3478

EpiCase AF: 0.0309

EpiControl AF: 0.0331

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	12
Dann	Benign	0.74
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.47	T;T;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-0.99	T
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.21	.;.;B;.
Vest4		0.11
MPC		0.18
ClinPred		0.0023	T
GERP RS		-0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.039
gMVP		0.15

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

Other links and lift over

dbSNP: rs11758242; hg19: chr6-31639845; COSMIC: COSV65498305; COSMIC: COSV65498305;