chr3-116445021-C-G

Variant names:

• chr3-116445021-C-G
• NM_002338.5:c.11G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002338.5(LSAMP):​c.11G>C​(p.Arg4Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,459,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LSAMP NM_002338.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.82
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2793672).

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.11G>C	p.Arg4Thr	missense	Exon 1 of 7	NP_002329.2
	LSAMP	NM_001318915.2		c.11G>C	p.Arg4Thr	missense	Exon 1 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.11G>C	p.Arg4Thr	missense	Exon 1 of 7	ENSP00000419000.1	Q13449
	LSAMP	ENST00000474851.1	TSL:5	c.179-66G>C		intron	N/A	ENSP00000418506.1	C9J5G3
	LSAMP	ENST00000717962.1		n.687-66G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1459930 Hom.: 0 Cov.: 33 AF XY: 0.00000551 AC XY: 4 AN XY: 725922

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.00 AC: 0 AN: 86178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110454

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		3.8
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Benign	0.14	T
Polyphen		0.91	P
Vest4		0.36
MutPred		0.61		Loss of MoRF binding (P = 0.0052)
MVP		0.33
MPC		1.3
ClinPred		0.59	D
GERP RS		3.9
PromoterAI		0.059	Neutral
Varity_R		0.071
gMVP		0.65
Mutation Taster		=87/13	polymorphism

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

hg19: chr3-116163868;