rs151059567

Variant names:

• chr3-183152460-G-A
• rs151059567
• NM_014398.4:c.803C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-183152460-G-A
• chr3-183152460-G-C

Variant summary

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

The NM_014398.4(LAMP3):​c.803C>T​(p.Thr268Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000608 in 1,612,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T268R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.28
• Publications: 5 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.803C>T	p.Thr268Met	missense_variant	Exon 3 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.803C>T	p.Thr268Met	missense_variant	Exon 4 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.803C>T	p.Thr268Met	missense_variant	Exon 3 of 6		XP_047303923.1
LAMP3	XM_011512688.3	c.803C>T	p.Thr268Met	missense_variant	Exon 3 of 6		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.803C>T	p.Thr268Met	missense_variant	Exon 3 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.731C>T	p.Thr244Met	missense_variant	Exon 3 of 6	2		ENSP00000418912.1

Frequencies

GnomAD3 genomes AF: 0.000296 AC: 45 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000140 AC: 35 AN: 250260 AF XY: 0.000133

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.000349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000363 AC: 53 AN: 1460726 Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16 AN XY: 726720

African (AFR) AF: 0.000659 AC: 22 AN: 33388

American (AMR) AF: 0.000247 AC: 11 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86130

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53402

Middle Eastern (MID) AF: 0.000177 AC: 1 AN: 5656

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111518

Other (OTH) AF: 0.000133 AC: 8 AN: 60334

GnomAD4 genome AF: 0.000296 AC: 45 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20 AN XY: 74452

African (AFR) AF: 0.000986 AC: 41 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000313 Hom.: 0

Bravo AF: 0.000340

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000173 AC: 21

EpiCase AF: 0.0000546

EpiControl AF: 0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.803C>T (p.T268M) alteration is located in exon 3 (coding exon 3) of the LAMP3 gene. This alteration results from a C to T substitution at nucleotide position 803, causing the threonine (T) at amino acid position 268 to be replaced by a methionine (M). 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	0.32
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	T;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.28	T
MutationAssessor	Pathogenic	3.4	M;.
PhyloP100		5.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.83
MVP		0.22
MPC		0.40
ClinPred		0.41	T
GERP RS		5.5
Varity_R		0.83
gMVP		0.20
Mutation Taster		=54/46	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs151059567; hg19: chr3-182870248; COSMIC: COSV55613491; COSMIC: COSV55613491;