3-183153897-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014398.4(LAMP3):c.544G>A(p.Gly182Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.405

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 -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0281955).
• BP6: Variant 3-183153897-C-T is Benign according to our data. Variant chr3-183153897-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2595323.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMP3	NM_014398.4	c.544G>A	p.Gly182Ser	missense_variant	2/6	ENST00000265598.8
LAMP3	XM_005247360.6	c.544G>A	p.Gly182Ser	missense_variant	3/7
LAMP3	XM_047447967.1	c.544G>A	p.Gly182Ser	missense_variant	2/6
LAMP3	XM_011512688.3	c.544G>A	p.Gly182Ser	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMP3	ENST00000265598.8	c.544G>A	p.Gly182Ser	missense_variant	2/6	1	NM_014398.4	P2
LAMP3	ENST00000466939.1	c.472G>A	p.Gly158Ser	missense_variant	2/6	2		A2
LAMP3	ENST00000470251.1			downstream_gene_variant		2
LAMP3	ENST00000476015.1			downstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152074 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000319 AC: 8 AN: 251150 Hom.: 0 AF XY: 0.0000295 AC XY: 4 AN XY: 135720

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000145

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000274 AC: 40 AN: 1461822 Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.0000828

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152074 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74280

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000328

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	0.11
Dann	Benign	0.41
DEOGEN2	Benign	0.10	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.028	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.027
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.010	B;.
Vest4		0.025
MVP		0.043
MPC		0.070
ClinPred		0.020	T
GERP RS		0.46
Varity_R		0.038
gMVP		0.12

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: rs774368709; hg19: chr3-182871685; COSMIC: COSV99660544; COSMIC: COSV99660544;