NM_002338.5:c.771G>A

Variant names:

• chr3-115841993-C-T
• NM_002338.5:c.771G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_002338.5(LSAMP):​c.771G>A​(p.Arg257Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LSAMP NM_002338.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.9329
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.47
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP6: Variant 3-115841993-C-T is Benign according to our data. Variant chr3-115841993-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3540922.Status of the report is criteria_provided_single_submitter, 1 stars.

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.771G>A	p.Arg257Arg	splice_region synonymous	Exon 6 of 7	NP_002329.2
	LSAMP	NM_001318915.2		c.771G>A	p.Arg257Arg	splice_region synonymous	Exon 6 of 9	NP_001305844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSAMP	ENST00000490035.7	TSL:1 MANE Select	c.771G>A	p.Arg257Arg	splice_region synonymous	Exon 6 of 7	ENSP00000419000.1	Q13449
	LSAMP	ENST00000333617.8	TSL:2	c.723G>A	p.Arg241Arg	splice_region synonymous	Exon 6 of 9	ENSP00000328455.4	H3BLU2
	LSAMP	ENST00000473171.5	TSL:3	n.218G>A		splice_region non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Benign	0.94
PhyloP100		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.93
dbscSNV1_RF	Pathogenic	0.74
SpliceAI score (max)		0.010		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

hg19: chr3-115560840; COSMIC: COSV61310942; COSMIC: COSV61310942;