3-116351316-T-C

Variant names:

• chr3-116351316-T-C
• rs7634137
• NM_002338.5:c.155+93561A>G

Variant summary

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

The NM_002338.5(LSAMP):​c.155+93561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,790 control chromosomes in the GnomAD database, including 11,879 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 0.33 (11879 hom., cov: 32)
• Consequence: LSAMP NM_002338.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 3 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]

LSAMP-AS1 (HGNC:40350): (LSAMP antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002338.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSAMP	NM_002338.5	MANE Select	c.155+93561A>G		intron	N/A	NP_002329.2
	LSAMP	NM_001318915.2		c.155+93561A>G		intron	N/A	NP_001305844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSAMP	ENST00000490035.7	TSL:1 MANE Select	c.155+93561A>G		intron	N/A	ENSP00000419000.1	Q13449
	LSAMP	ENST00000333617.8	TSL:2	c.107+93561A>G		intron	N/A	ENSP00000328455.4	H3BLU2
	LSAMP	ENST00000474851.1	TSL:5	c.257+93561A>G		intron	N/A	ENSP00000418506.1	C9J5G3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49913 AN: 151672 Hom.: 11842 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.329 AC: 49991 AN: 151790 Hom.: 11879 Cov.: 32 AF XY: 0.320 AC XY: 23769 AN XY: 74164

African (AFR) AF: 0.677 AC: 28008 AN: 41386

American (AMR) AF: 0.259 AC: 3935 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 945 AN: 3466

East Asian (EAS) AF: 0.128 AC: 659 AN: 5166

South Asian (SAS) AF: 0.205 AC: 988 AN: 4814

European-Finnish (FIN) AF: 0.123 AC: 1301 AN: 10570

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.195 AC: 13236 AN: 67868

Other (OTH) AF: 0.322 AC: 677 AN: 2104

Alfa AF: 0.227 Hom.: 8428

Bravo AF: 0.354

Asia WGS AF: 0.221 AC: 766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		-1.5
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7634137;

hg19: chr3-116070163;