chr6-31707988-G-A

Variant names:

• chr6-31707988-G-A
• rs2242653
• NM_001003693.3:c.500G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 55 publications found

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:38821): (LY6G6F-LY6G6D readthrough) This locus represents naturally occurring readthrough transcription between the neighboring LY6G6F (lymphocyte antigen 6 family member G6F) and LY6G6D (lymphocyte antigen 6 family member G6D) genes on chromosome 6. The readthrough transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Jul 2017]

ENSG00000204422 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LY6G6F	NM_001003693.3	c.500G>A	p.Arg167Lys	missense_variant	Exon 3 of 6	ENST00000375832.5	NP_001003693.1
LY6G6F-LY6G6D	NM_001353334.2	c.500G>A	p.Arg167Lys	missense_variant	Exon 3 of 6		NP_001340263.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6G6F	ENST00000375832.5	c.500G>A	p.Arg167Lys	missense_variant	Exon 3 of 6	1	NM_001003693.3	ENSP00000364992.5
LY6G6F-LY6G6D	ENST00000503322.1	c.500G>A	p.Arg167Lys	missense_variant	Exon 3 of 6	1		ENSP00000421232.1
ENSG00000204422	ENST00000461287.1	n.537+4029C>T		intron_variant	Intron 3 of 21	2

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

GnomAD2 exomes AF: 0.169 AC: 41685 AN: 246648 AF XY: 0.164

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 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

African (AFR) AF: 0.0866 AC: 2899 AN: 33480

American (AMR) AF: 0.234 AC: 10454 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 1080 AN: 26136

East Asian (EAS) AF: 0.219 AC: 8675 AN: 39698

South Asian (SAS) AF: 0.145 AC: 12504 AN: 86258

European-Finnish (FIN) AF: 0.315 AC: 16468 AN: 52308

Middle Eastern (MID) AF: 0.0693 AC: 400 AN: 5768

European-Non Finnish (NFE) AF: 0.145 AC: 161711 AN: 1111998

Other (OTH) AF: 0.139 AC: 8402 AN: 60386

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

African (AFR) AF: 0.0996 AC: 4137 AN: 41546

American (AMR) AF: 0.202 AC: 3084 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3470

East Asian (EAS) AF: 0.154 AC: 797 AN: 5174

South Asian (SAS) AF: 0.150 AC: 726 AN: 4830

European-Finnish (FIN) AF: 0.333 AC: 3518 AN: 10570

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10406 AN: 67986

Other (OTH) AF: 0.122 AC: 256 AN: 2106

Alfa AF: 0.147 Hom.: 8285

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;.
PhyloP100		-0.72
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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