rs150432783

Variant names:

• chr3-183135834-C-G
• rs150432783
• NM_014398.4:c.1000G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-183135834-C-G
• chr3-183135834-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014398.4(LAMP3):​c.1000G>C​(p.Gly334Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,590 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.1000G>C	p.Gly334Arg	missense_variant	Exon 5 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.1000G>C	p.Gly334Arg	missense_variant	Exon 6 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.1106G>C	p.Arg369Pro	missense_variant	Exon 6 of 6		XP_047303923.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.1000G>C	p.Gly334Arg	missense_variant	Exon 5 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.928G>C	p.Gly310Arg	missense_variant	Exon 5 of 6	2		ENSP00000418912.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251348 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461590 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727102

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

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	Pathogenic	0.74
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	T;T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-7.0	D;D
REVEL	Uncertain	0.37
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.80
MutPred		0.91		Gain of MoRF binding (P = 0.0152);.;
MVP		0.43
MPC		0.45
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.93
gMVP		0.25

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: rs150432783; hg19: chr3-182853622;