3-183135882-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014398.4(LAMP3):​c.952A>G​(p.Ile318Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,611,228 control chromosomes in the GnomAD database, including 403,688 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.59 (29354 hom., cov: 31)
  • Exomes 𝑓: 0.71 (374334 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.6672607E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

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>G	p.Ile318Val	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>G	p.Ile318Val	missense	Exon 5 of 6	ENSP00000265598.3	Q9UQV4
	LAMP3	ENST00000948307.1		c.952A>G	p.Ile318Val	missense	Exon 5 of 7	ENSP00000618366.1
	LAMP3	ENST00000466939.1	TSL:2	c.880A>G	p.Ile294Val	missense	Exon 5 of 6	ENSP00000418912.1	E7ETP9

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89469 AN: 151892 Hom.: 29369 Cov.: 31

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.636

GnomAD2 exomes AF: 0.649 AC: 163032 AN: 251102 AF XY: 0.666

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.485

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.508

Gnomad FIN exome AF: 0.768

Gnomad NFE exome AF: 0.734

Gnomad OTH exome AF: 0.678

GnomAD4 exome AF: 0.709 AC: 1035093 AN: 1459218 Hom.: 374334 Cov.: 34 AF XY: 0.711 AC XY: 516276 AN XY: 726032

African (AFR) AF: 0.271 AC: 9056 AN: 33418

American (AMR) AF: 0.491 AC: 21940 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 19865 AN: 26098

East Asian (EAS) AF: 0.451 AC: 17892 AN: 39666

South Asian (SAS) AF: 0.682 AC: 58834 AN: 86204

European-Finnish (FIN) AF: 0.760 AC: 40578 AN: 53404

Middle Eastern (MID) AF: 0.647 AC: 3726 AN: 5760

European-Non Finnish (NFE) AF: 0.740 AC: 821670 AN: 1109666

Other (OTH) AF: 0.689 AC: 41532 AN: 60298

GnomAD4 genome AF: 0.589 AC: 89477 AN: 152010 Hom.: 29354 Cov.: 31 AF XY: 0.589 AC XY: 43767 AN XY: 74318

African (AFR) AF: 0.291 AC: 12060 AN: 41448

American (AMR) AF: 0.550 AC: 8406 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2630 AN: 3466

East Asian (EAS) AF: 0.491 AC: 2533 AN: 5160

South Asian (SAS) AF: 0.674 AC: 3245 AN: 4812

European-Finnish (FIN) AF: 0.765 AC: 8086 AN: 10576

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50323 AN: 67958

Other (OTH) AF: 0.633 AC: 1335 AN: 2110

Alfa AF: 0.684 Hom.: 130115

Bravo AF: 0.560

TwinsUK AF: 0.743 AC: 2755

ALSPAC AF: 0.745 AC: 2871

ESP6500AA AF: 0.301 AC: 1327

ESP6500EA AF: 0.740 AC: 6366

ExAC AF: 0.648 AC: 78667

Asia WGS AF: 0.560 AC: 1947 AN: 3478

EpiCase AF: 0.736

EpiControl AF: 0.740

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.35
DANN	Benign	0.27
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0000037	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.32	N
PhyloP100		-0.65
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.017
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.059
ClinPred		0.0022	T
GERP RS		-1.4
Varity_R		0.018
gMVP		0.035
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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; COSMIC: COSV55616290;