rs12493050

chr3-183147285-G-Achr3-183147285-G-Cchr3-183147285-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014398.4(LAMP3):c.888+5090C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 151,860 control chromosomes in the GnomAD database, including 42,736 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (42736 hom., cov: 29)
• Consequence: LAMP3 NM_014398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMP3	NM_014398.4	c.888+5090C>T		intron_variant		ENST00000265598.8
LAMP3	XM_005247360.6	c.888+5090C>T		intron_variant
LAMP3	XM_011512688.3	c.888+5090C>T		intron_variant
LAMP3	XM_047447967.1	c.888+5090C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMP3	ENST00000265598.8	c.888+5090C>T		intron_variant		1	NM_014398.4	P2
LAMP3	ENST00000466939.1	c.816+5090C>T		intron_variant		2		A2

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113392 AN: 151740 Hom.: 42714 Cov.: 29

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.752

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.747 AC: 113475 AN: 151860 Hom.: 42736 Cov.: 29 AF XY: 0.749 AC XY: 55606 AN XY: 74226

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.766

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.798

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.753

Alfa AF: 0.783 Hom.: 27578

Bravo AF: 0.740

Asia WGS AF: 0.767 AC: 2666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.2
Dann	Benign	0.66

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

Other links and lift over

dbSNP: rs12493050; hg19: chr3-182865073;