chr8-74029040-C-G

Variant summary

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

The NM_015364.5(LY96):ā€‹c.469C>Gā€‹(p.Pro157Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,986 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. 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. P157L) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

LY96
NM_015364.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.200
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]

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=0.09599525).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LY96NM_015364.5 linkuse as main transcriptc.469C>G p.Pro157Ala missense_variant 5/5 ENST00000284818.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LY96ENST00000284818.7 linkuse as main transcriptc.469C>G p.Pro157Ala missense_variant 5/51 NM_015364.5 P1Q9Y6Y9-1
LY96ENST00000518893.1 linkuse as main transcriptc.379C>G p.Pro127Ala missense_variant 4/43 Q9Y6Y9-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151986
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
27
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151986
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74242
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.089
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
13
DANN
Benign
0.89
DEOGEN2
Benign
0.36
T;.
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.53
T;T
M_CAP
Benign
0.0061
T
MetaRNN
Benign
0.096
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-2.3
N;D
REVEL
Benign
0.036
Sift
Benign
0.067
T;T
Sift4G
Benign
0.098
T;T
Polyphen
0.19
B;.
Vest4
0.28
MutPred
0.19
Loss of glycosylation at P157 (P = 0.0432);.;
MVP
0.55
MPC
0.11
ClinPred
0.090
T
GERP RS
3.3
Varity_R
0.23
gMVP
0.67

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs11466004; hg19: chr8-74941275; API