Genetic Variant LAMP3:p.Met242Ile (chr3-183153715-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014398.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP3	NM_014398.4	MANE Select	c.726G>A	p.Met242Ile	missense	Exon 2 of 6	NP_055213.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMP3	ENST00000265598.8	TSL:1 MANE Select	c.726G>A	p.Met242Ile	missense	Exon 2 of 6	ENSP00000265598.3	Q9UQV4
LAMP3	ENST00000948307.1		c.726G>A	p.Met242Ile	missense	Exon 2 of 7	ENSP00000618366.1
LAMP3	ENST00000466939.1	TSL:2	c.654G>A	p.Met218Ile	missense	Exon 2 of 6	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

GnomAD2 exomes

AF:

0.0000492

AC:

AN:

182904

AF XY:

0.0000313

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 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

African (AFR)

AF:

0.000196

AC:

AN:

30594

American (AMR)

AF:

0.0000322

AC:

AN:

31020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20202

East Asian (EAS)

AF:

0.00

AC:

AN:

39016

South Asian (SAS)

AF:

0.00

AC:

AN:

71124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5338

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

1071528

Other (OTH)

AF:

0.0000177

AC:

AN:

56610

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000145

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000482

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000169

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.71

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.3

PhyloP100

4.3

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.30

Sift

Uncertain

0.019

Sift4G

Pathogenic

0.0

Polyphen

0.96

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

Mutation Taster

=42/58

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over