3-183152401-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014398.4(LAMP3):c.862G>A(p.Gly288Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,611,534 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 (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

LAMP3
NM_014398.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.07

Publications

1 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.874

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4 link	c.862G>A	p.Gly288Arg	missense_variant	Exon 3 of 6	ENST00000265598.8	NP_055213.2	Q9UQV4
LAMP3	XM_005247360.6 link	c.862G>A	p.Gly288Arg	missense_variant	Exon 4 of 7		XP_005247417.1
LAMP3	XM_047447967.1 link	c.862G>A	p.Gly288Arg	missense_variant	Exon 3 of 6		XP_047303923.1
LAMP3	XM_011512688.3 link	c.862G>A	p.Gly288Arg	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 link	c.862G>A	p.Gly288Arg	missense_variant	Exon 3 of 6	1	NM_014398.4	ENSP00000265598.3		Q9UQV4
LAMP3	ENST00000466939.1 link	c.790G>A	p.Gly264Arg	missense_variant	Exon 3 of 6	2		ENSP00000418912.1		E7ETP9

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

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:

0.00000402

AC:

AN:

248882

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000294

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000110

AC:

AN:

1459418

Hom.:

Cov.:

AF XY:

0.00000964

AC XY:

AN XY:

726084

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33274

American (AMR)

AF:

0.0000226

AC:

AN:

44304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26046

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.00

AC:

AN:

85918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00000630

AC:

AN:

1111018

Other (OTH)

AF:

0.0000166

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152116

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.862G>A (p.G288R) alteration is located in exon 3 (coding exon 3) of the LAMP3 gene. This alteration results from a G to A substitution at nucleotide position 862, causing the glycine (G) at amino acid position 288 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

See cases

Uncertain:1

Hadassah Hebrew University Medical Center

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.37

T;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.8

M;.

PhyloP100

4.1

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Uncertain

0.39

Sift

Uncertain

0.0060

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.93

MutPred

0.74

Gain of methylation at G288 (P = 0.0183);.;

MVP

0.60

MPC

0.45

ClinPred

0.92

GERP RS

5.4

Varity_R

0.97

gMVP

0.35

Mutation Taster

=53/47

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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.

3-183152401-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over