Variant 3-116019580-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000490035.7(LSAMP):c.449C>T(p.Thr150Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,052 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

LSAMP
ENST00000490035.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

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:

LOC124906269 (HGNC:):

LOC124906269 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSAMP	NM_002338.5 linkuse as main transcript	c.449C>T	p.Thr150Ile	missense_variant	3/7	ENST00000490035.7	NP_002329.2
LOC124906269	XR_007096010.1 linkuse as main transcript	n.208+12295G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LSAMP	ENST00000490035.7 linkuse as main transcript	c.449C>T	p.Thr150Ile	missense_variant	3/7	1	NM_002338.5	ENSP00000419000	P1
LSAMP	ENST00000333617.8 linkuse as main transcript	c.401C>T	p.Thr134Ile	missense_variant	3/9	2		ENSP00000328455
LSAMP	ENST00000474851.1 linkuse as main transcript	c.551C>T	p.Thr184Ile	missense_variant	5/5	5		ENSP00000418506
LSAMP	ENST00000498645.1 linkuse as main transcript	n.158C>T		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460794

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726750

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.449C>T (p.T150I) alteration is located in exon 3 (coding exon 3) of the LSAMP gene. This alteration results from a C to T substitution at nucleotide position 449, causing the threonine (T) at amino acid position 150 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

Pathogenic

0.61

BayesDel_addAF

Uncertain

0.046

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.34

.;T;.;T

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-0.39

MutationAssessor

Benign

1.9

.;L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.3

.;D;D;D

REVEL

Benign

0.25

Sift

Benign

0.13

.;T;D;D

Sift4G

Uncertain

0.0060

D;D;D;.

Polyphen

0.77

.;P;.;.

Vest4

0.77

MutPred

0.55

.;Loss of disorder (P = 0.0841);.;.;

MVP

0.44

MPC

1.4

ClinPred

0.99

GERP RS

5.9

Varity_R

0.41

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over