rs763705634

Variant names:

• chr13-113309848-A-G
• rs763705634
• NM_005561.4:c.389A>G

Your query was ambiguous. Multiple possible variants found:

• chr13-113309848-A-G
• chr13-113309848-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_005561.4(LAMP1):​c.389A>G​(p.Asn130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,612,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N130I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: LAMP1 NM_005561.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

Genes affected

LAMP1 (HGNC:6499): (lysosomal associated membrane protein 1) The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may also play a role in tumor cell metastasis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) (polylactosaminoglycan) asparagine (size 0) in uniprot entity LAMP1_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2903094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP1	NM_005561.4	c.389A>G	p.Asn130Ser	missense_variant	Exon 3 of 9	ENST00000332556.5	NP_005552.3
LAMP1	XM_011537494.3	c.332A>G	p.Asn111Ser	missense_variant	Exon 3 of 9		XP_011535796.1
LAMP1	XM_047430302.1	c.323A>G	p.Asn108Ser	missense_variant	Exon 3 of 9		XP_047286258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP1	ENST00000332556.5	c.389A>G	p.Asn130Ser	missense_variant	Exon 3 of 9	1	NM_005561.4	ENSP00000333298.4
LAMP1	ENST00000472564.1	n.1881A>G		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000361 AC: 9 AN: 249340 AF XY: 0.0000370

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000442

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1460252 Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18 AN XY: 726470

African (AFR) AF: 0.000120 AC: 4 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4762

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111678

Other (OTH) AF: 0.0000498 AC: 3 AN: 60264

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152238 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74372

African (AFR) AF: 0.000145 AC: 6 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000869

ExAC AF: 0.0000579 AC: 7

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 04, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.389A>G (p.N130S) alteration is located in exon 3 (coding exon 3) of the LAMP1 gene. This alteration results from a A to G substitution at nucleotide position 389, causing the asparagine (N) at amino acid position 130 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.091
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.2
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.060
Sift	Benign	0.046	D
Sift4G	Benign	0.32	T
Polyphen		0.29	B
Vest4		0.21
MVP		0.50
MPC		0.37
ClinPred		0.17	T
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.060
gMVP		0.38
Mutation Taster		=84/16	polymorphism

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: rs763705634; hg19: chr13-113964163;