3-183153744-C-A

Variant names:

• chr3-183153744-C-A
• rs1430999134
• NM_014398.4:c.697G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014398.4(LAMP3):​c.697G>T​(p.Gly233*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,389,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LAMP3 NM_014398.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.697G>T	p.Gly233*	stop_gained	Exon 2 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.697G>T	p.Gly233*	stop_gained	Exon 3 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.697G>T	p.Gly233*	stop_gained	Exon 2 of 6		XP_047303923.1
LAMP3	XM_011512688.3	c.697G>T	p.Gly233*	stop_gained	Exon 2 of 6		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.697G>T	p.Gly233*	stop_gained	Exon 2 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.625G>T	p.Gly209*	stop_gained	Exon 2 of 6	2		ENSP00000418912.1
LAMP3	ENST00000476015.1	c.*157G>T		downstream_gene_variant		4		ENSP00000419059.1
LAMP3	ENST00000470251.1	c.*196G>T		downstream_gene_variant		2		ENSP00000420589.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.19e-7 AC: 1 AN: 1389896 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 683982

African (AFR) AF: 0.00 AC: 0 AN: 31170

American (AMR) AF: 0.00 AC: 0 AN: 33706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20862

East Asian (EAS) AF: 0.00 AC: 0 AN: 39234

South Asian (SAS) AF: 0.0000137 AC: 1 AN: 72730

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5402

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078910

Other (OTH) AF: 0.00 AC: 0 AN: 57322

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.98
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.92	D
PhyloP100		2.8
Vest4		0.81
GERP RS		5.8
Mutation Taster		=41/159	disease causing (fs/PTC)

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

Other links and lift over

dbSNP: rs1430999134; hg19: chr3-182871532;