3-183135882-T-C

Position:

• chr3-183135882-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.952A>G	p.Ile318Val	missense_variant	5/6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.952A>G	p.Ile318Val	missense_variant	6/7		XP_005247417.1
LAMP3	XM_047447967.1	c.1058A>G	p.Asn353Ser	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>G	p.Ile318Val	missense_variant	5/6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.880A>G	p.Ile294Val	missense_variant	5/6	2		ENSP00000418912.1

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

GnomAD3 exomes AF: 0.649 AC: 163032 AN: 251102 Hom.: 55378 AF XY: 0.666 AC XY: 90356 AN XY: 135710

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 SAS exome AF: 0.677

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

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.761

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.760

Gnomad4 NFE exome AF: 0.740

Gnomad4 OTH exome AF: 0.689

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

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.633

Alfa AF: 0.706 Hom.: 96269

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 v4.3

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;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0000037	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.32	N;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.16	N;N
REVEL	Benign	0.017
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs482912; hg19: chr3-182853670; COSMIC: COSV55616290;