Variant 3-183152460-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000265598.8(LAMP3):c.803C>G(p.Thr268Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. T268M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LAMP3
ENST00000265598.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

Variant links:

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]

LAMP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.982

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LAMP3	NM_014398.4 linkuse as main transcript	c.803C>G	p.Thr268Arg	missense_variant	3/6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6 linkuse as main transcript	c.803C>G	p.Thr268Arg	missense_variant	4/7		XP_005247417.1
LAMP3	XM_047447967.1 linkuse as main transcript	c.803C>G	p.Thr268Arg	missense_variant	3/6		XP_047303923.1
LAMP3	XM_011512688.3 linkuse as main transcript	c.803C>G	p.Thr268Arg	missense_variant	3/6		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8 linkuse as main transcript	c.803C>G	p.Thr268Arg	missense_variant	3/6	1	NM_014398.4	ENSP00000265598	P2
LAMP3	ENST00000466939.1 linkuse as main transcript	c.731C>G	p.Thr244Arg	missense_variant	3/6	2		ENSP00000418912	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000200

AC:

AN:

250260

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000274

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460726

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726720

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

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.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 07, 2024

The c.803C>G (p.T268R) alteration is located in exon 3 (coding exon 3) of the LAMP3 gene. This alteration results from a C to G substitution at nucleotide position 803, causing the threonine (T) at amino acid position 268 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

Pathogenic

0.82

BayesDel_addAF

Uncertain

0.071

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

T;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.036

MetaRNN

Pathogenic

0.98

D;D

MetaSVM

Benign

-0.39

MutationAssessor

Pathogenic

3.4

M;.

MutationTaster

Benign

0.71

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.89

MutPred

0.88

Gain of solvent accessibility (P = 0.0171);.;

MVP

0.29

MPC

0.37

ClinPred

0.82

GERP RS

5.5

Varity_R

0.96

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over