chr3-116019562-T-C

Position:

• chr3-116019562-T-C

Variant summary

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

The NM_002338.5(LSAMP):​c.467A>G​(p.Asn156Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,644 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000027 (0 hom.)
• Consequence: LSAMP NM_002338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51

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 (HGNC:):

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=0.2540499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.467A>G	p.Asn156Ser	missense_variant	3/7	ENST00000490035.7	NP_002329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.467A>G	p.Asn156Ser	missense_variant	3/7	1	NM_002338.5	ENSP00000419000.1
LSAMP	ENST00000333617.8	c.419A>G	p.Asn140Ser	missense_variant	3/9	2		ENSP00000328455.4
LSAMP	ENST00000474851.1	c.569A>G	p.Asn190Ser	missense_variant	5/5	5		ENSP00000418506.1
LSAMP	ENST00000498645.1	n.176A>G		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460644 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726672

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

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

Jan 04, 2022

The c.467A>G (p.N156S) alteration is located in exon 3 (coding exon 3) of the LSAMP gene. This alteration results from a A to G substitution at nucleotide position 467, causing the asparagine (N) at amino acid position 156 to be replaced by a serine (S). 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	0.071
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	.;T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.49	.;N;.;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.35	.;N;N;N
REVEL	Benign	0.095
Sift	Benign	0.38	.;T;T;T
Sift4G	Benign	0.54	T;T;T;.
Polyphen		0.0090	.;B;.;.
Vest4		0.22
MutPred		0.28		.;Gain of glycosylation at N156 (P = 0.0071);.;.;
MVP		0.38
MPC		0.39
ClinPred		0.54	D
GERP RS		3.5
Varity_R		0.045
gMVP		0.15

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

Other links and lift over

dbSNP: rs1940580416; hg19: chr3-115738409;