3-115875328-G-A

Variant names:

• chr3-115875328-G-A
• rs10511351
• NM_002338.5:c.515-22711C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002338.5(LSAMP):​c.515-22711C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,064 control chromosomes in the GnomAD database, including 1,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1562 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.908
• Publications: 2 publications found

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]

ENSG00000297708 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSAMP	NM_002338.5	c.515-22711C>T		intron_variant	Intron 3 of 6	ENST00000490035.7	NP_002329.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LSAMP	ENST00000490035.7	c.515-22711C>T		intron_variant	Intron 3 of 6	1	NM_002338.5	ENSP00000419000.1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18702 AN: 151946 Hom.: 1563 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18696 AN: 152064 Hom.: 1562 Cov.: 32 AF XY: 0.121 AC XY: 9000 AN XY: 74326

African (AFR) AF: 0.0317 AC: 1317 AN: 41518

American (AMR) AF: 0.112 AC: 1711 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3472

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5168

South Asian (SAS) AF: 0.0653 AC: 315 AN: 4822

European-Finnish (FIN) AF: 0.164 AC: 1729 AN: 10564

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12773 AN: 67952

Other (OTH) AF: 0.117 AC: 246 AN: 2110

Alfa AF: 0.165 Hom.: 3706

Bravo AF: 0.115

Asia WGS AF: 0.0310 AC: 109 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	14
DANN	Benign	0.74
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10511351; hg19: chr3-115594175;