Variant 3-183153954-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014398.4(LAMP3):c.487A>G(p.Ser163Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

LAMP3
NM_014398.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.783

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049234807).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4 link	c.487A>G	p.Ser163Gly	missense_variant	Exon 2 of 6	ENST00000265598.8	NP_055213.2	Q9UQV4
LAMP3	XM_005247360.6 link	c.487A>G	p.Ser163Gly	missense_variant	Exon 3 of 7		XP_005247417.1
LAMP3	XM_047447967.1 link	c.487A>G	p.Ser163Gly	missense_variant	Exon 2 of 6		XP_047303923.1
LAMP3	XM_011512688.3 link	c.487A>G	p.Ser163Gly	missense_variant	Exon 2 of 6		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMP3	ENST00000265598.8 link	c.487A>G	p.Ser163Gly	missense_variant	Exon 2 of 6	1	NM_014398.4	ENSP00000265598.3	Q9UQV4
LAMP3	ENST00000466939.1 link	c.415A>G	p.Ser139Gly	missense_variant	Exon 2 of 6	2		ENSP00000418912.1	E7ETP9
LAMP3	ENST00000476015.1 link	c.487A>G	p.Ser163Gly	missense_variant	Exon 3 of 3	4		ENSP00000419059.1	C9JYP5
LAMP3	ENST00000470251.1 link	c.415A>G	p.Ser139Gly	missense_variant	Exon 3 of 3	2		ENSP00000420589.1	C9JDI8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251488

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Feb 03, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.487A>G (p.S163G) alteration is located in exon 2 (coding exon 2) of the LAMP3 gene. This alteration results from a A to G substitution at nucleotide position 487, causing the serine (S) at amino acid position 163 to be replaced by a glycine (G). 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

0.058

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.2

DANN

Benign

0.48

DEOGEN2

Benign

0.13

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.54

T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

N;.;.;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.78

N;N;N;N

REVEL

Benign

0.012

Sift

Benign

0.81

T;T;T;T

Sift4G

Benign

0.72

T;T;T;T

Polyphen

0.0020

B;.;.;.

Vest4

0.041

MutPred

0.37

Gain of relative solvent accessibility (P = 0.0166);.;Gain of relative solvent accessibility (P = 0.0166);.;

MVP

0.068

MPC

0.070

ClinPred

0.0080

GERP RS

-2.1

Varity_R

0.030

gMVP

0.24

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

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