3-116019618-G-C

Variant names:

• chr3-116019618-G-C
• NM_002338.5:c.411C>G

Variant summary

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

The NM_002338.5(LSAMP):​c.411C>G​(p.Ile137Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSAMP NM_002338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.285

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]

LOC124906269 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.411C>G	p.Ile137Met	missense_variant	Exon 3 of 7	ENST00000490035.7	NP_002329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.411C>G	p.Ile137Met	missense_variant	Exon 3 of 7	1	NM_002338.5	ENSP00000419000.1
LSAMP	ENST00000333617.8	c.363C>G	p.Ile121Met	missense_variant	Exon 3 of 9	2		ENSP00000328455.4
LSAMP	ENST00000474851.1	c.513C>G	p.Ile171Met	missense_variant	Exon 5 of 5	5		ENSP00000418506.1
LSAMP	ENST00000498645.1	n.120C>G		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 17, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.411C>G (p.I137M) alteration is located in exon 3 (coding exon 3) of the LSAMP gene. This alteration results from a C to G substitution at nucleotide position 411, causing the isoleucine (I) at amino acid position 137 to be replaced by a methionine (M). 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	0.22
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;T;.;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.0	.;L;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	.;D;D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.021	.;D;D;D
Sift4G	Uncertain	0.010	D;D;D;.
Polyphen		0.90	.;P;.;.
Vest4		0.65
MutPred		0.45		.;Gain of disorder (P = 0.0615);.;.;
MVP		0.65
MPC		1.4
ClinPred		0.95	D
GERP RS		0.94
Varity_R		0.46
gMVP		0.46

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: chr3-115738465;