chr3-116086360-C-T

Position:

• chr3-116086360-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002338.5(LSAMP):​c.352G>A​(p.Glu118Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSAMP NM_002338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

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]

ACMG classification

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=0.12786728).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.352G>A	p.Glu118Lys	missense_variant	2/7	ENST00000490035.7	NP_002329.2
LSAMP	NM_001318915.2	c.352G>A	p.Glu118Lys	missense_variant	2/9		NP_001305844.1
LSAMP	XM_017006383.3	c.352G>A	p.Glu118Lys	missense_variant	2/8		XP_016861872.1
LSAMP	XM_011512840.4	c.352G>A	p.Glu118Lys	missense_variant	2/8		XP_011511142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.352G>A	p.Glu118Lys	missense_variant	2/7	1	NM_002338.5	ENSP00000419000.1
LSAMP	ENST00000333617.8	c.304G>A	p.Glu102Lys	missense_variant	2/9	2		ENSP00000328455.4
LSAMP	ENST00000474851.1	c.454G>A	p.Glu152Lys	missense_variant	4/5	5		ENSP00000418506.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2024

The c.352G>A (p.E118K) 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 352, causing the glutamic acid (E) at amino acid position 118 to be replaced by a lysine (K). 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	0.19
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	.;T;.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	0.035
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.65	.;N;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.040	.;N;N;N
REVEL	Benign	0.17
Sift	Benign	1.0	.;T;T;T
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.0030	.;B;.;.
Vest4		0.29
MutPred		0.47		.;Gain of methylation at E118 (P = 0.0123);.;.;
MVP		0.22
MPC		0.63
ClinPred		0.95	D
GERP RS		4.9
Varity_R		0.20
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-115805207;