6-31672202-C-T

Position:

• chr6-31672202-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.526C>T​(p.Arg176Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0683 in 1,612,998 control chromosomes in the GnomAD database, including 4,242 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 0.078 (513 hom., cov: 32)
  • Exomes 𝑓: 0.067 (3729 hom.)
• Consequence: LY6G5B NM_021221.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584

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=0.0018301308).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY6G5B	NM_021221.3	c.526C>T	p.Arg176Cys	missense_variant	3/3	ENST00000375864.5	NP_067044.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY6G5B	ENST00000375864.5	c.526C>T	p.Arg176Cys	missense_variant	3/3	1	NM_021221.3	ENSP00000365024	P1
LY6G5B	ENST00000409525.1	c.361C>T	p.Arg121Cys	missense_variant	2/2	1		ENSP00000386365

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11892 AN: 152090 Hom.: 514 Cov.: 32

Gnomad AFR AF: 0.0939

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0589

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0724

Gnomad OTH AF: 0.0773

GnomAD3 exomes AF: 0.0738 AC: 18193 AN: 246644 Hom.: 785 AF XY: 0.0759 AC XY: 10203 AN XY: 134422

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0441

Gnomad ASJ exome AF: 0.0600

Gnomad EAS exome AF: 0.0907

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.0807

Gnomad NFE exome AF: 0.0694

Gnomad OTH exome AF: 0.0691

GnomAD4 exome AF: 0.0673 AC: 98325 AN: 1460790 Hom.: 3729 Cov.: 32 AF XY: 0.0685 AC XY: 49781 AN XY: 726712

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0465

Gnomad4 ASJ exome AF: 0.0595

Gnomad4 EAS exome AF: 0.0436

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0793

Gnomad4 NFE exome AF: 0.0648

Gnomad4 OTH exome AF: 0.0655

GnomAD4 genome AF: 0.0781 AC: 11889 AN: 152208 Hom.: 513 Cov.: 32 AF XY: 0.0789 AC XY: 5872 AN XY: 74412

Gnomad4 AFR AF: 0.0936

Gnomad4 AMR AF: 0.0513

Gnomad4 ASJ AF: 0.0589

Gnomad4 EAS AF: 0.0723

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0820

Gnomad4 NFE AF: 0.0724

Gnomad4 OTH AF: 0.0764

Alfa AF: 0.0727 Hom.: 854

Bravo AF: 0.0771

TwinsUK AF: 0.0550 AC: 204

ALSPAC AF: 0.0584 AC: 225

ESP6500AA AF: 0.0956 AC: 289

ESP6500EA AF: 0.0698 AC: 378

ExAC AF: 0.0760 AC: 8980

Asia WGS AF: 0.0760 AC: 264 AN: 3478

EpiCase AF: 0.0716

EpiControl AF: 0.0705

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.26	.;.;T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.71	T;T;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;.;L;.
PROVEAN	Uncertain	-2.4	.;.;N;D
REVEL	Benign	0.059
Sift	Benign	0.11	.;.;T;T
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	.;.;D;.
Vest4		0.13
MPC		0.16
ClinPred		0.024	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.10
gMVP		0.24

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: rs9267532; hg19: chr6-31639979; COSMIC: COSV65498141; COSMIC: COSV65498141;