Variant 3-183153715-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014398.4(LAMP3):c.726G>A(p.Met242Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000327 in 1,527,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

LAMP3
NM_014398.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.30

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4 link	c.726G>A	p.Met242Ile	missense_variant	Exon 2 of 6	ENST00000265598.8	NP_055213.2	Q9UQV4
LAMP3	XM_005247360.6 link	c.726G>A	p.Met242Ile	missense_variant	Exon 3 of 7		XP_005247417.1
LAMP3	XM_047447967.1 link	c.726G>A	p.Met242Ile	missense_variant	Exon 2 of 6		XP_047303923.1
LAMP3	XM_011512688.3 link	c.726G>A	p.Met242Ile	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 link	c.726G>A	p.Met242Ile	missense_variant	Exon 2 of 6	1	NM_014398.4	ENSP00000265598.3		Q9UQV4
LAMP3	ENST00000466939.1 link	c.654G>A	p.Met218Ile	missense_variant	Exon 2 of 6	2		ENSP00000418912.1		E7ETP9

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000492

AC:

AN:

182904

Hom.:

AF XY:

0.0000313

AC XY:

AN XY:

95846

show subpopulations

Gnomad AFR exome

AF:

0.000388

Gnomad AMR exome

AF:

0.0000443

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000227

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000204

AC:

AN:

1375538

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

674960

show subpopulations

Gnomad4 AFR exome

AF:

0.000196

Gnomad4 AMR exome

AF:

0.0000322

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000187

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

AF:

0.000145

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000169

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.726G>A (p.M242I) alteration is located in exon 2 (coding exon 2) of the LAMP3 gene. This alteration results from a G to A substitution at nucleotide position 726, causing the methionine (M) at amino acid position 242 to be replaced by an isoleucine (I). 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

0.72

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.3

M;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.4

D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.019

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.96

P;.

Vest4

0.50

MutPred

0.72

Loss of ubiquitination at K239 (P = 0.1091);.;

MVP

0.19

MPC

0.38

ClinPred

0.76

GERP RS

5.8

Varity_R

0.85

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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