3-183135882-T-G

Variant names:

• chr3-183135882-T-G
• rs482912
• NM_014398.4:c.952A>C

Variant summary

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

The NM_014398.4(LAMP3):​c.952A>C​(p.Ile318Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 46 publications found

Genes affected

LAMP3 (HGNC:14582): (lysosomal associated membrane protein 3) Dendritic cells (DCs) are the most potent antigen-presenting cells. Immature DCs efficiently capture antigens and differentiate into interdigitating dendritic cells (IDCs) in lymphoid tissues that induce primary T-cell responses (summary by de Saint-Vis et al., 1998 [PubMed 9768752]).[supplied by OMIM, Dec 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=0.21050996).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014398.4. 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
	LAMP3	NM_014398.4	MANE Select	c.952A>C	p.Ile318Leu	missense	Exon 5 of 6	NP_055213.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP3	ENST00000265598.8	TSL:1 MANE Select	c.952A>C	p.Ile318Leu	missense	Exon 5 of 6	ENSP00000265598.3	Q9UQV4
	LAMP3	ENST00000948307.1		c.952A>C	p.Ile318Leu	missense	Exon 5 of 7	ENSP00000618366.1
	LAMP3	ENST00000466939.1	TSL:2	c.880A>C	p.Ile294Leu	missense	Exon 5 of 6	ENSP00000418912.1	E7ETP9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.0
DANN	Benign	0.80
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.65
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.0080
Sift	Benign	0.31	T
Sift4G	Benign	0.28	T
Polyphen		0.0060	B
Vest4		0.17
MutPred		0.42		Loss of catalytic residue at I318 (P = 0.0649)
MVP		0.068
MPC		0.072
ClinPred		0.040	T
GERP RS		-1.4
Varity_R		0.064
gMVP		0.058
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs482912; hg19: chr3-182853670;