rs1163515349

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005561.4(LAMP1):​c.10C>T​(p.Pro4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000303 in 1,090,428 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 (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

LAMP1
NM_005561.4 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.309

Publications

1 publications found
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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=0.12788948).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMP1NM_005561.4 linkc.10C>T p.Pro4Ser missense_variant Exon 1 of 9 ENST00000332556.5 NP_005552.3 P11279-1A0A024RDY3
LAMP1XM_047430302.1 linkc.-299C>T upstream_gene_variant XP_047286258.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMP1ENST00000332556.5 linkc.10C>T p.Pro4Ser missense_variant Exon 1 of 9 1 NM_005561.4 ENSP00000333298.4 P11279-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151916
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
4160
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000320
AC:
30
AN:
938512
Hom.:
0
Cov.:
13
AF XY:
0.0000263
AC XY:
12
AN XY:
456684
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
19586
American (AMR)
AF:
0.00
AC:
0
AN:
8790
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
13368
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25744
South Asian (SAS)
AF:
0.00
AC:
0
AN:
23530
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
21658
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2628
European-Non Finnish (NFE)
AF:
0.0000382
AC:
30
AN:
784522
Other (OTH)
AF:
0.00
AC:
0
AN:
38686
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.520
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
151916
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74208
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41426
American (AMR)
AF:
0.000131
AC:
2
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5188
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10488
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67940
Other (OTH)
AF:
0.00
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 24, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.10C>T (p.P4S) alteration is located in exon 1 (coding exon 1) of the LAMP1 gene. This alteration results from a C to T substitution at nucleotide position 10, causing the proline (P) at amino acid position 4 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
0.081
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.32
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.44
T
M_CAP
Pathogenic
0.43
D
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.34
N
PhyloP100
0.31
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.051
Sift
Benign
0.26
T
Sift4G
Benign
0.41
T
Polyphen
0.044
B
Vest4
0.12
MutPred
0.28
Gain of phosphorylation at P4 (P = 0.0323);
MVP
0.20
MPC
0.28
ClinPred
0.11
T
GERP RS
1.1
PromoterAI
0.17
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.038
gMVP
0.40
Mutation Taster
=97/3
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

Publications

Other links and lift over

dbSNP: rs1163515349; hg19: chr13-113951759; API