Variant 8-74010049-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015364.5(LY96):c.251C>T(p.Thr84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,456,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

LY96
NM_015364.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

LY96 (HGNC:17156): (lymphocyte antigen 96) This gene encodes a protein which associates with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccyaride (LPS), thus providing a link between the receptor and LPS signaling. Studies of the mouse ortholog suggest that this gene may be involved in endotoxin neutralization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2010]

LY96 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16416225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LY96	NM_015364.5 linkuse as main transcript	c.251C>T	p.Thr84Ile	missense_variant	3/5	ENST00000284818.7	NP_056179.4	Q9Y6Y9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LY96	ENST00000284818.7 linkuse as main transcript	c.251C>T	p.Thr84Ile	missense_variant	3/5	1	NM_015364.5	ENSP00000284818.2		Q9Y6Y9-1
LY96	ENST00000518893.1 linkuse as main transcript	c.161C>T	p.Thr54Ile	missense_variant	2/4	3		ENSP00000430533.1		Q9Y6Y9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251324

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1456998

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.03e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

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

Nov 30, 2022

The c.251C>T (p.T84I) alteration is located in exon 3 (coding exon 3) of the LY96 gene. This alteration results from a C to T substitution at nucleotide position 251, causing the threonine (T) at amino acid position 84 to be replaced by an isoleucine (I). 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

Benign

0.26

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;.

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.42

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-2.8

D;N

REVEL

Benign

0.23

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.031

B;.

Vest4

0.34

MutPred

0.47

Gain of sheet (P = 0.0221);.;

MVP

0.81

MPC

0.11

ClinPred

0.55

GERP RS

4.1

Varity_R

0.25

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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