rs759022817

Variant names:

Variant summary

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

The NM_002338.5(LSAMP):c.284G>A(p.Ser95Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,826 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: 0.0000082 ( 0 hom. )

Consequence

LSAMP
NM_002338.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

Publications

1 publications found

Variant links:

Genes affected

LSAMP (HGNC:6705): (limbic system associated membrane protein) This gene encodes a member of the immunoglobulin LAMP, OBCAM and neurotrimin (IgLON) family of proteins. The encoded preproprotein is proteolytically processed to generate a neuronal surface glycoprotein. This protein may act as a selective homophilic adhesion molecule during axon guidance and neuronal growth in the developing limbic system. The encoded protein may also function as a tumor suppressor and may play a role in neuropsychiatric disorders. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

LSAMP links:

ENSG00000297753 (HGNC:):

ENSG00000297753 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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5 link	c.284G>A	p.Ser95Asn	missense_variant	Exon 2 of 7	ENST00000490035.7	NP_002329.2	Q13449B7Z661
LSAMP	NM_001318915.2 link	c.284G>A	p.Ser95Asn	missense_variant	Exon 2 of 9		NP_001305844.1	Q13449B7Z661
LSAMP	XM_017006383.3 link	c.284G>A	p.Ser95Asn	missense_variant	Exon 2 of 8		XP_016861872.1
LSAMP	XM_011512840.4 link	c.284G>A	p.Ser95Asn	missense_variant	Exon 2 of 8		XP_011511142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7 link	c.284G>A	p.Ser95Asn	missense_variant	Exon 2 of 7	1	NM_002338.5	ENSP00000419000.1		Q13449

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251352

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111950

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 18, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.284G>A (p.S95N) alteration is located in exon 2 (coding exon 2) of the LSAMP gene. This alteration results from a G to A substitution at nucleotide position 284, causing the serine (S) at amino acid position 95 to be replaced by an asparagine (N). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.0039

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

.;T;.;T

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.69

D;D;D;D

MetaSVM

Uncertain

0.022

MutationAssessor

Uncertain

2.3

.;M;.;.

PhyloP100

7.9

PrimateAI

Pathogenic

0.79

PROVEAN

Uncertain

-2.5

.;D;D;D

REVEL

Uncertain

0.50

Sift

Uncertain

0.0010

.;D;D;T

Sift4G

Benign

0.097

T;T;T;.

Polyphen

1.0

.;D;.;.

Vest4

0.74

MVP

0.64

MPC

1.3

ClinPred

0.80

GERP RS

5.8

PromoterAI

0.019

Neutral

(source)

Varity_R

0.68

gMVP

0.93

Mutation Taster

=54/46

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over