rs111542625

Variant names:

• chr3-183153785-T-C
• rs111542625
• NM_014398.4:c.656A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014398.4(LAMP3):​c.656A>G​(p.Gln219Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000272 in 1,579,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.135
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038416952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.656A>G	p.Gln219Arg	missense_variant	Exon 2 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.656A>G	p.Gln219Arg	missense_variant	Exon 3 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.656A>G	p.Gln219Arg	missense_variant	Exon 2 of 6		XP_047303923.1
LAMP3	XM_011512688.3	c.656A>G	p.Gln219Arg	missense_variant	Exon 2 of 6		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.656A>G	p.Gln219Arg	missense_variant	Exon 2 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.584A>G	p.Gln195Arg	missense_variant	Exon 2 of 6	2		ENSP00000418912.1
LAMP3	ENST00000476015.1	c.*116A>G		downstream_gene_variant		4		ENSP00000419059.1
LAMP3	ENST00000470251.1	c.*155A>G		downstream_gene_variant		2		ENSP00000420589.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000271 AC: 6 AN: 221572 AF XY: 0.0000170

Gnomad AFR exome AF: 0.000188

Gnomad AMR exome AF: 0.0000647

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000984

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000252 AC: 36 AN: 1427564 Hom.: 0 Cov.: 31 AF XY: 0.0000212 AC XY: 15 AN XY: 706168

African (AFR) AF: 0.000428 AC: 14 AN: 32708

American (AMR) AF: 0.0000488 AC: 2 AN: 40994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23466

East Asian (EAS) AF: 0.00 AC: 0 AN: 39472

South Asian (SAS) AF: 0.00 AC: 0 AN: 79028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5610

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1095396

Other (OTH) AF: 0.000305 AC: 18 AN: 58952

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74442

African (AFR) AF: 0.000168 AC: 7 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000437 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.656A>G (p.Q219R) alteration is located in exon 2 (coding exon 2) of the LAMP3 gene. This alteration results from a A to G substitution at nucleotide position 656, causing the glutamine (Q) at amino acid position 219 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.0
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.
PhyloP100		0.14
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.11
Sift	Benign	0.25	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.82	P;.
Vest4		0.046
MVP		0.11
MPC		0.094
ClinPred		0.093	T
GERP RS		-0.34
Varity_R		0.22
gMVP		0.14
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: rs111542625; hg19: chr3-182871573;