3-183153694-T-C

Variant names:

• chr3-183153694-T-C
• rs112754078
• NM_014398.4:c.747A>G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014398.4(LAMP3):​c.747A>G​(p.Gln249Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: LAMP3 NM_014398.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=0.312 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.747A>G	p.Gln249Gln	synonymous_variant	Exon 2 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.747A>G	p.Gln249Gln	synonymous_variant	Exon 3 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.747A>G	p.Gln249Gln	synonymous_variant	Exon 2 of 6		XP_047303923.1
LAMP3	XM_011512688.3	c.747A>G	p.Gln249Gln	synonymous_variant	Exon 2 of 6		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.747A>G	p.Gln249Gln	synonymous_variant	Exon 2 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.675A>G	p.Gln225Gln	synonymous_variant	Exon 2 of 6	2		ENSP00000418912.1
LAMP3	ENST00000476015.1	c.*207A>G		downstream_gene_variant		4		ENSP00000419059.1
LAMP3	ENST00000470251.1	c.*246A>G		downstream_gene_variant		2		ENSP00000420589.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.4
DANN	Benign	0.50

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: rs112754078; hg19: chr3-182871482;