rs112754078

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-183153694-T-A
• chr3-183153694-T-C
• chr3-183153694-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014398.4(LAMP3):​c.747A>T​(p.Gln249His) variant causes a missense 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. 12/21 in silico tools predict 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 missense
• 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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34716332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.747A>T	p.Gln249His	missense_variant	Exon 2 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.747A>T	p.Gln249His	missense_variant	Exon 3 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.747A>T	p.Gln249His	missense_variant	Exon 2 of 6		XP_047303923.1
LAMP3	XM_011512688.3	c.747A>T	p.Gln249His	missense_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>T	p.Gln249His	missense_variant	Exon 2 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.675A>T	p.Gln225His	missense_variant	Exon 2 of 6	2		ENSP00000418912.1
LAMP3	ENST00000476015.1	c.*207A>T		downstream_gene_variant		4		ENSP00000419059.1
LAMP3	ENST00000470251.1	c.*246A>T		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
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	0.029
Eigen_PC	Benign	-0.10
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.60	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.016	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		1.0	D;.
Vest4		0.28
MutPred		0.67		Gain of methylation at K251 (P = 0.1049);.;
MVP		0.18
MPC		0.39
ClinPred		0.90	D
GERP RS		-1.3
Varity_R		0.41
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-182871482;