Variant 3-115852506-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002338.5(LSAMP):c.626A>G(p.Lys209Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,460,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LSAMP
NM_002338.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16202852).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSAMP	NM_002338.5 link	c.626A>G	p.Lys209Arg	missense_variant	4/7	ENST00000490035.7	NP_002329.2	Q13449B7Z661

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LSAMP	ENST00000490035.7 link	c.626A>G	p.Lys209Arg	missense_variant	4/7	1	NM_002338.5	ENSP00000419000.1	Q13449
LSAMP	ENST00000333617.8 link	c.578A>G	p.Lys193Arg	missense_variant	4/9	2		ENSP00000328455.4	H3BLU2
LSAMP	ENST00000473171.5 link	n.73A>G		non_coding_transcript_exon_variant	1/3	3
LSAMP	ENST00000498645.1 link	n.335A>G		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249706

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134992

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000550

Gnomad SAS 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:

0.00000205

AC:

AN:

1460546

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726562

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:

0.0000375

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Oct 07, 2024

The c.626A>G (p.K209R) alteration is located in exon 4 (coding exon 4) of the LSAMP gene. This alteration results from a A to G substitution at nucleotide position 626, causing the lysine (K) at amino acid position 209 to be replaced by an arginine (R). 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

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.40

DEOGEN2

Benign

0.081

.;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.037

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.30

.;N;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.080

.;N;N

REVEL

Benign

0.16

Sift

Benign

1.0

.;T;T

Sift4G

Benign

0.98

T;T;T

Polyphen

0.064

.;B;.

Vest4

0.079

MutPred

0.39

.;Loss of ubiquitination at K209 (P = 0.0134);.;

MVP

0.61

MPC

1.0

ClinPred

0.65

GERP RS

5.0

Varity_R

0.14

gMVP

0.56

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