3-183153511-T-G

Variant names:

• chr3-183153511-T-G
• rs6414500
• NM_014398.4:c.759+171A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014398.4(LAMP3):​c.759+171A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 152,170 control chromosomes in the GnomAD database, including 59,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.88 (59491 hom., cov: 32)
• Consequence: LAMP3 NM_014398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.759+171A>C		intron_variant	Intron 2 of 5	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.759+171A>C		intron_variant	Intron 3 of 6		XP_005247417.1
LAMP3	XM_047447967.1	c.759+171A>C		intron_variant	Intron 2 of 5		XP_047303923.1
LAMP3	XM_011512688.3	c.759+171A>C		intron_variant	Intron 2 of 5		XP_011510990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP3	ENST00000265598.8	c.759+171A>C		intron_variant	Intron 2 of 5	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.687+171A>C		intron_variant	Intron 2 of 5	2		ENSP00000418912.1

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134393 AN: 152052 Hom.: 59457 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.873

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.879

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.893

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.884 AC: 134482 AN: 152170 Hom.: 59491 Cov.: 32 AF XY: 0.884 AC XY: 65764 AN XY: 74398

African (AFR) AF: 0.838 AC: 34764 AN: 41484

American (AMR) AF: 0.873 AC: 13352 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3078 AN: 3472

East Asian (EAS) AF: 0.898 AC: 4647 AN: 5176

South Asian (SAS) AF: 0.878 AC: 4238 AN: 4826

European-Finnish (FIN) AF: 0.916 AC: 9691 AN: 10582

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61688 AN: 68028

Other (OTH) AF: 0.894 AC: 1883 AN: 2106

Alfa AF: 0.897 Hom.: 42546

Bravo AF: 0.880

Asia WGS AF: 0.879 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.52
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6414500; hg19: chr3-182871299;