rs2242653

Positions:

• chr6-31707988-G-A

Variant summary

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

The NM_001003693.3(LY6G6F):​c.500G>A​(p.Arg167Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,612,924 control chromosomes in the GnomAD database, including 20,791 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.15 (2073 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18718 hom.)
• Consequence: LY6G6F NM_001003693.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.723

Genes affected

LY6G6F (HGNC:13933): (lymphocyte antigen 6 family member G6F) The human G6f protein is a type I transmembrane protein belonging to the immunoglobin (Ig) superfamily, which is comprised of cell-surface proteins involved in the immune system and cellular recognition (de Vet et al., 2003 [PubMed 12852788]).[supplied by OMIM, Mar 2008]

LY6G6F-LY6G6D (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023539662).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LY6G6F	NM_001003693.3	c.500G>A	p.Arg167Lys	missense_variant	3/6	ENST00000375832.5
LY6G6F-LY6G6D	NM_001353334.2	c.500G>A	p.Arg167Lys	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LY6G6F	ENST00000375832.5	c.500G>A	p.Arg167Lys	missense_variant	3/6	1	NM_001003693.3	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23193 AN: 152056 Hom.: 2068 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.169 AC: 41685 AN: 246648 Hom.: 4177 AF XY: 0.164 AC XY: 22031 AN XY: 134408

Gnomad AFR exome AF: 0.0994

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.0395

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.152 AC: 222593 AN: 1460750 Hom.: 18718 Cov.: 35 AF XY: 0.151 AC XY: 109734 AN XY: 726686

Gnomad4 AFR exome AF: 0.0866

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.0413

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.139

GnomAD4 genome AF: 0.153 AC: 23219 AN: 152174 Hom.: 2073 Cov.: 32 AF XY: 0.161 AC XY: 11949 AN XY: 74378

Gnomad4 AFR AF: 0.0996

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.122

Alfa AF: 0.143 Hom.: 3434

Bravo AF: 0.141

TwinsUK AF: 0.141 AC: 523

ALSPAC AF: 0.136 AC: 526

ESP6500AA AF: 0.100 AC: 303

ESP6500EA AF: 0.152 AC: 823

ExAC AF: 0.163 AC: 19389

Asia WGS AF: 0.176 AC: 610 AN: 3478

EpiCase AF: 0.132

EpiControl AF: 0.134

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.74
DEOGEN2	Benign	0.0038	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.45	T;.
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.18	N;N
REVEL	Benign	0.051
Sift	Benign	0.86	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0020	B;.
Vest4		0.038
MPC		0.074
ClinPred		0.0014	T
GERP RS		0.87
Varity_R		0.038
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242653; hg19: chr6-31675765; COSMIC: COSV65442766; COSMIC: COSV65442766;