Genetic Variant LAMP1:p.Ala2Val (chr13-113297439-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005561.4(LAMP1):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 892,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LAMP1
NM_005561.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Publications

0 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]

LAMP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005561.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP1	NM_005561.4	MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 9	NP_005552.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LAMP1	ENST00000332556.5	TSL:1 MANE Select	c.5C>T	p.Ala2Val	missense	Exon 1 of 9	ENSP00000333298.4	P11279-1
LAMP1	ENST00000886119.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 10	ENSP00000556178.1
LAMP1	ENST00000886115.1		c.5C>T	p.Ala2Val	missense	Exon 1 of 9	ENSP00000556174.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

4860

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:

0.0000134

AC:

AN:

892864

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

435896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18656

American (AMR)

AF:

0.00

AC:

AN:

8680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12990

East Asian (EAS)

AF:

0.0000791

AC:

AN:

25270

South Asian (SAS)

AF:

0.00

AC:

AN:

22692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21508

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2490

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

743490

Other (OTH)

AF:

0.00

AC:

AN:

37088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

0.036

Eigen_PC

Benign

-0.040

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.67

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PhyloP100

1.6

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.95

REVEL

Benign

0.063

Sift

Uncertain

0.015

Sift4G

Benign

0.21

Polyphen

0.99

Vest4

0.31

MutPred

0.30

Loss of disorder (P = 0.0812)

MVP

0.27

MPC

0.72

ClinPred

0.58

GERP RS

1.2

PromoterAI

-0.24

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.075

gMVP

0.55

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over