chr13-113310807-G-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005561.4(LAMP1):​c.502G>A​(p.Val168Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,840 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

LAMP1
NM_005561.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.34

Publications

4 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: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036124438).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMP1NM_005561.4 linkc.502G>A p.Val168Ile missense_variant Exon 4 of 9 ENST00000332556.5 NP_005552.3 P11279-1A0A024RDY3
LAMP1XM_011537494.3 linkc.445G>A p.Val149Ile missense_variant Exon 4 of 9 XP_011535796.1
LAMP1XM_047430302.1 linkc.436G>A p.Val146Ile missense_variant Exon 4 of 9 XP_047286258.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMP1ENST00000332556.5 linkc.502G>A p.Val168Ile missense_variant Exon 4 of 9 1 NM_005561.4 ENSP00000333298.4 P11279-1
LAMP1ENST00000472564.1 linkn.1994G>A non_coding_transcript_exon_variant Exon 3 of 6 2

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152032
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000160
AC:
4
AN:
249506
AF XY:
0.0000296
show subpopulations
Gnomad AFR exome
AF:
0.0000642
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:
0.0000265
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1461690
Hom.:
0
Cov.:
33
AF XY:
0.0000426
AC XY:
31
AN XY:
727144
show subpopulations
African (AFR)
AF:
0.000149
AC:
5
AN:
33480
American (AMR)
AF:
0.0000447
AC:
2
AN:
44708
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39696
South Asian (SAS)
AF:
0.0000232
AC:
2
AN:
86246
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53362
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.0000360
AC:
40
AN:
1111910
Other (OTH)
AF:
0.0000497
AC:
3
AN:
60386
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.457
Heterozygous variant carriers
0
3
6
8
11
14
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:
0.0000329
AC:
5
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74380
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41508
American (AMR)
AF:
0.000262
AC:
4
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10576
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
68010
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.545
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.00
Hom.:
0
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 14, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.502G>A (p.V168I) alteration is located in exon 4 (coding exon 4) of the LAMP1 gene. This alteration results from a G to A substitution at nucleotide position 502, causing the valine (V) at amino acid position 168 to be replaced by an isoleucine (I). 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
0.071
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
0.043
DANN
Benign
0.84
DEOGEN2
Benign
0.11
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.054
N
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.036
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L
PhyloP100
-1.3
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.49
N
REVEL
Benign
0.010
Sift
Benign
0.33
T
Sift4G
Benign
0.46
T
Polyphen
0.19
B
Vest4
0.076
MVP
0.29
MPC
0.24
ClinPred
0.043
T
GERP RS
-3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.018
gMVP
0.18
Mutation Taster
=94/6
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: rs191812061; hg19: chr13-113965122; COSMIC: COSV60211240; API