rs482912

Positions:

• chr3-183135882-T-A
• chr3-183135882-T-C
• chr3-183135882-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000265598.8(LAMP3):​c.952A>T​(p.Ile318Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. I318V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LAMP3 ENST00000265598.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.952A>T	p.Ile318Phe	missense_variant	5/6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.952A>T	p.Ile318Phe	missense_variant	6/7		XP_005247417.1
LAMP3	XM_047447967.1	c.1058A>T	p.Asn353Ile	missense_variant	6/6		XP_047303923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.952A>T	p.Ile318Phe	missense_variant	5/6	1	NM_014398.4	ENSP00000265598	P2
LAMP3	ENST00000466939.1	c.880A>T	p.Ile294Phe	missense_variant	5/6	2		ENSP00000418912	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1460808 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726756

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.3
DANN	Benign	0.76
DEOGEN2	Benign	0.15	T;T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	4.5e-21	P;P
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.044
Sift	Benign	0.15	T;T
Sift4G	Uncertain	0.043	D;T
Polyphen		0.51	P;.
Vest4		0.16
MutPred		0.59		Gain of ubiquitination at K323 (P = 0.0882);.;
MVP		0.068
MPC		0.13
ClinPred		0.15	T
GERP RS		-1.4
Varity_R		0.082
gMVP		0.063

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

Publications

LitVar

Other links and lift over

dbSNP: rs482912; hg19: chr3-182853670;