3-183135884-G-C

Variant names:

• chr3-183135884-G-C
• rs761547141
• NM_014398.4:c.950C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014398.4(LAMP3):​c.950C>G​(p.Thr317Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T317I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LAMP3 NM_014398.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09104985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP3	NM_014398.4	c.950C>G	p.Thr317Arg	missense_variant	Exon 5 of 6	ENST00000265598.8	NP_055213.2
LAMP3	XM_005247360.6	c.950C>G	p.Thr317Arg	missense_variant	Exon 6 of 7		XP_005247417.1
LAMP3	XM_047447967.1	c.1056C>G	p.Asp352Glu	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.950C>G	p.Thr317Arg	missense_variant	Exon 5 of 6	1	NM_014398.4	ENSP00000265598.3
LAMP3	ENST00000466939.1	c.878C>G	p.Thr293Arg	missense_variant	Exon 5 of 6	2		ENSP00000418912.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460198 Hom.: 0 Cov.: 29 AF XY: 0.00000275 AC XY: 2 AN XY: 726504

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1110478

Other (OTH) AF: 0.00 AC: 0 AN: 60336

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.39
DANN	Benign	0.22
DEOGEN2	Benign	0.12	T;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.29	N;.
PhyloP100		-0.25
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.070	N;N
REVEL	Benign	0.031
Sift	Benign	0.52	T;T
Sift4G	Benign	0.62	T;T
Polyphen		0.0	B;.
Vest4		0.081
MutPred		0.55		Gain of sheet (P = 0.0827);.;
MVP		0.043
MPC		0.077
ClinPred		0.019	T
GERP RS		-5.2
Varity_R		0.068
gMVP		0.11
Mutation Taster		=78/22	polymorphism

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: rs761547141; hg19: chr3-182853672;