NM_014398.4:c.809C>G

Variant names:

• chr3-183152454-G-C
• rs1576885548
• NM_014398.4:c.809C>G

Variant summary

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

The NM_014398.4(LAMP3):​c.809C>G​(p.Ala270Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,860 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.965

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=0.33370537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.809C>G	p.Ala270Gly	missense_variant	Exon 3 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.809C>G	p.Ala270Gly	missense_variant	Exon 4 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.809C>G	p.Ala270Gly	missense_variant	Exon 3 of 6		XP_047303923.1
LAMP3	XM_011512688.3	c.809C>G	p.Ala270Gly	missense_variant	Exon 3 of 6		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.809C>G	p.Ala270Gly	missense_variant	Exon 3 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.737C>G	p.Ala246Gly	missense_variant	Exon 3 of 6	2		ENSP00000418912.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460860 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726796

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000505

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T;T
Eigen	Benign	-0.025
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.069
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		0.90	P;.
Vest4		0.40
MutPred		0.73		Gain of disorder (P = 0.0794);.;
MVP		0.15
MPC		0.18
ClinPred		0.95	D
GERP RS		2.8
Varity_R		0.74
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1576885548; hg19: chr3-182870242;