rs6414498

Variant names:

• chr3-183153426-T-G
• rs6414498
• NM_014398.4:c.759+256A>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+256A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,146 control chromosomes in the GnomAD database, including 61,866 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 0.90 (61866 hom., cov: 31)
• Consequence: LAMP3 NM_014398.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 6 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=-0.7).
• 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+256A>C		intron_variant	Intron 2 of 5	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.759+256A>C		intron_variant	Intron 3 of 6		XP_005247417.1
LAMP3	XM_047447967.1	c.759+256A>C		intron_variant	Intron 2 of 5		XP_047303923.1
LAMP3	XM_011512688.3	c.759+256A>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+256A>C		intron_variant	Intron 2 of 5	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.687+256A>C		intron_variant	Intron 2 of 5	2		ENSP00000418912.1

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137089 AN: 152028 Hom.: 61826 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.955

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.880

Gnomad FIN AF: 0.916

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.903

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

GnomAD4 genome AF: 0.902 AC: 137182 AN: 152146 Hom.: 61866 Cov.: 31 AF XY: 0.900 AC XY: 66985 AN XY: 74388

African (AFR) AF: 0.901 AC: 37409 AN: 41508

American (AMR) AF: 0.878 AC: 13405 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3076 AN: 3468

East Asian (EAS) AF: 0.898 AC: 4636 AN: 5164

South Asian (SAS) AF: 0.879 AC: 4234 AN: 4818

European-Finnish (FIN) AF: 0.916 AC: 9687 AN: 10580

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61693 AN: 68028

Other (OTH) AF: 0.904 AC: 1900 AN: 2102

Alfa AF: 0.901 Hom.: 11560

Bravo AF: 0.900

Asia WGS AF: 0.881 AC: 3062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.8
DANN	Benign	0.83
PhyloP100		-0.23
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: rs6414498; hg19: chr3-182871214;