rs148728376

Variant names:

• chr8-143021655-A-G
• rs148728376
• NM_002346.3:c.262A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-143021655-A-G
• chr8-143021655-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002346.3(LY6E):​c.262A>G​(p.Met88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. M88L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LY6E NM_002346.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 0 publications found

Genes affected

LY6E (HGNC:6727): (lymphocyte antigen 6 family member E) This gene belongs to the human Ly6 gene family and encodes a glycosylphosphatidyl-inositol (GPI)-anchored cell surface protein. The protein plays an important role in T cell physiology, oncogenesis and immunological regulation. The protein is also involved in modulation of viral infection by coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2. [provided by RefSeq, Aug 2021]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0336881).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LY6E	NM_002346.3	c.262A>G	p.Met88Val	missense_variant	Exon 4 of 4	ENST00000292494.11	NP_002337.1
LY6E	NM_001127213.2	c.262A>G	p.Met88Val	missense_variant	Exon 4 of 4		NP_001120685.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LY6E	ENST00000292494.11	c.262A>G	p.Met88Val	missense_variant	Exon 4 of 4	1	NM_002346.3	ENSP00000292494.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251384 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461526 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727080

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53068

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.47
DANN	Benign	0.61
DEOGEN2	Benign	0.088	T;T;T;T;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.51	.;.;.;.;.;.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.034	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N;N;N;N;N;N;N
PhyloP100		-0.12
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.30	N;N;N;N;N;N;N
REVEL	Benign	0.023
Sift	Benign	1.0	T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Polyphen		0.0	B;B;B;B;B;B;B
Vest4		0.068
MutPred		0.36		Gain of catalytic residue at M88 (P = 0.0252);Gain of catalytic residue at M88 (P = 0.0252);Gain of catalytic residue at M88 (P = 0.0252);Gain of catalytic residue at M88 (P = 0.0252);Gain of catalytic residue at M88 (P = 0.0252);Gain of catalytic residue at M88 (P = 0.0252);Gain of catalytic residue at M88 (P = 0.0252);
MVP		0.38
MPC		0.42
ClinPred		0.025	T
GERP RS		0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.023
gMVP		0.24
Mutation Taster		=99/1	polymorphism

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: rs148728376; hg19: chr8-144103072;