Variant 3-183152454-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000265598.8(LAMP3):c.809C>A(p.Ala270Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,860 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. A270T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LAMP3
ENST00000265598.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.965

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LAMP3	NM_014398.4 linkuse as main transcript	c.809C>A	p.Ala270Asp	missense_variant	3/6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6 linkuse as main transcript	c.809C>A	p.Ala270Asp	missense_variant	4/7		XP_005247417.1
LAMP3	XM_047447967.1 linkuse as main transcript	c.809C>A	p.Ala270Asp	missense_variant	3/6		XP_047303923.1
LAMP3	XM_011512688.3 linkuse as main transcript	c.809C>A	p.Ala270Asp	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.809C>A	p.Ala270Asp	missense_variant	3/6	1	NM_014398.4	ENSP00000265598	P2
LAMP3	ENST00000466939.1 linkuse as main transcript	c.737C>A	p.Ala246Asp	missense_variant	3/6	2		ENSP00000418912	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460860

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000673

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 15, 2021

The c.809C>A (p.A270D) alteration is located in exon 3 (coding exon 3) of the LAMP3 gene. This alteration results from a C to A substitution at nucleotide position 809, causing the alanine (A) at amino acid position 270 to be replaced by an aspartic acid (D). 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

0.64

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Benign

0.046

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.98

D;.

Vest4

0.70

MutPred

0.75

Gain of disorder (P = 0.0575);.;

MVP

0.14

MPC

0.35

ClinPred

0.96

GERP RS

2.8

Varity_R

0.77

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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