NM_015364.5:c.470C>T

Variant names:

• chr8-74029041-C-T
• rs1054044936
• NM_015364.5:c.470C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015364.5(LY96):​c.470C>T​(p.Pro157Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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)
• Consequence: LY96 NM_015364.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.967
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14772037).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015364.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY96	NM_015364.5	MANE Select	c.470C>T	p.Pro157Leu	missense	Exon 5 of 5	NP_056179.4	Q9Y6Y9-1
	LY96	NM_001195797.2		c.380C>T	p.Pro127Leu	missense	Exon 4 of 4	NP_001182726.1	Q9Y6Y9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LY96	ENST00000284818.7	TSL:1 MANE Select	c.470C>T	p.Pro157Leu	missense	Exon 5 of 5	ENSP00000284818.2	Q9Y6Y9-1
	LY96	ENST00000518893.1	TSL:3	c.380C>T	p.Pro127Leu	missense	Exon 4 of 4	ENSP00000430533.1	Q9Y6Y9-2
	LY96	ENST00000962532.1		c.341C>T	p.Pro114Leu	missense	Exon 4 of 4	ENSP00000632591.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.97
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.036
Sift	Benign	0.055	T
Sift4G	Uncertain	0.058	T
Polyphen		0.95	P
Vest4		0.34
MutPred		0.24		Loss of glycosylation at P157 (P = 0.0432)
MVP		0.68
MPC		0.35
ClinPred		0.87	D
GERP RS		2.0
Varity_R		0.24
gMVP		0.76
Mutation Taster		=97/3	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: rs1054044936; hg19: chr8-74941276;