Variant 6-6649634-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000230568.5(LY86):c.362A>G(p.Tyr121Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,566,798 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0015 ( 4 hom. )

Consequence

LY86
ENST00000230568.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84

Variant links:

Genes affected

LY86 (HGNC:16837): (lymphocyte antigen 86) Acts upstream of or within positive regulation of lipopolysaccharide-mediated signaling pathway. Predicted to be located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

LY86 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17063391).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY86	NM_004271.4 linkuse as main transcript	c.362A>G	p.Tyr121Cys	missense_variant	4/5	ENST00000230568.5	NP_004262.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY86	ENST00000230568.5 linkuse as main transcript	c.362A>G	p.Tyr121Cys	missense_variant	4/5	1	NM_004271.4	ENSP00000230568	P1
LY86	ENST00000379953.6 linkuse as main transcript	c.362A>G	p.Tyr121Cys	missense_variant	5/6	5		ENSP00000369286	P1

Frequencies

GnomAD3 genomes

AF:

0.00111

AC:

169

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00203

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00105

AC:

253

AN:

242014

Hom.:

AF XY:

0.00104

AC XY:

136

AN XY:

130822

show subpopulations

Gnomad AFR exome

AF:

0.000436

Gnomad AMR exome

AF:

0.000595

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000357

Gnomad FIN exome

AF:

0.000440

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00153

AC:

2163

AN:

1414444

Hom.:

Cov.:

AF XY:

0.00151

AC XY:

1067

AN XY:

705952

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

Gnomad4 AMR exome

AF:

0.000570

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000338

Gnomad4 FIN exome

AF:

0.000331

Gnomad4 NFE exome

AF:

0.00186

Gnomad4 OTH exome

AF:

0.00150

GnomAD4 genome

AF:

0.00111

AC:

169

AN:

152354

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00203

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00174

Hom.:

Bravo

AF:

0.00104

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00111

AC:

135

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00231

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 28, 2022

The c.362A>G (p.Y121C) alteration is located in exon 4 (coding exon 4) of the LY86 gene. This alteration results from a A to G substitution at nucleotide position 362, causing the tyrosine (Y) at amino acid position 121 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.67

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.69

D;D

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.18

Sift

Benign

0.055

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.67

MVP

0.58

MPC

0.054

ClinPred

0.029

GERP RS

5.1

Varity_R

0.46

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over