3-183154047-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014398.4(LAMP3):c.394T>G(p.Tyr132Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 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: 6.8e-7 (0 hom.)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.528

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]

ACMG classification

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=0.05716464).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMP3	NM_014398.4	c.394T>G	p.Tyr132Asp	missense_variant	2/6	ENST00000265598.8
LAMP3	XM_005247360.6	c.394T>G	p.Tyr132Asp	missense_variant	3/7
LAMP3	XM_047447967.1	c.394T>G	p.Tyr132Asp	missense_variant	2/6
LAMP3	XM_011512688.3	c.394T>G	p.Tyr132Asp	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMP3	ENST00000265598.8	c.394T>G	p.Tyr132Asp	missense_variant	2/6	1	NM_014398.4	P2
LAMP3	ENST00000466939.1	c.322T>G	p.Tyr108Asp	missense_variant	2/6	2		A2
LAMP3	ENST00000476015.1	c.394T>G	p.Tyr132Asp	missense_variant	3/3	4
LAMP3	ENST00000470251.1	c.322T>G	p.Tyr108Asp	missense_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.394T>G (p.Y132D) alteration is located in exon 2 (coding exon 2) of the LAMP3 gene. This alteration results from a T to G substitution at nucleotide position 394, causing the tyrosine (Y) at amino acid position 132 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	Benign	0.065
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	1.1
Dann	Benign	0.63
DEOGEN2	Benign	0.12	T;T;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.76	N;N;N;N
REVEL	Benign	0.014
Sift	Benign	0.20	T;T;T;T
Sift4G	Benign	0.64	T;T;T;T
Polyphen		0.020	B;.;.;.
Vest4		0.13
MutPred		0.41		Loss of phosphorylation at Y132 (P = 0.012);.;Loss of phosphorylation at Y132 (P = 0.012);.;
MVP		0.043
MPC		0.15
ClinPred		0.047	T
GERP RS		-2.3
Varity_R		0.056
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-182871835;