3-50286838-G-C

Variant names:

• chr3-50286838-G-C
• rs147348613
• NM_153215.3:c.337G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_153215.3(LSMEM2):​c.337G>C​(p.Ala113Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LSMEM2 NM_153215.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 3 publications found

Genes affected

LSMEM2 (HGNC:26781): (leucine rich single-pass membrane protein 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153215.3. 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
	LSMEM2	NM_153215.3	MANE Select	c.337G>C	p.Ala113Pro	missense	Exon 3 of 4	NP_694947.1	Q8N112
	LSMEM2	NM_001304385.2		c.334G>C	p.Ala112Pro	missense	Exon 3 of 4	NP_001291314.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LSMEM2	ENST00000316436.4	TSL:1 MANE Select	c.337G>C	p.Ala113Pro	missense	Exon 3 of 4	ENSP00000315081.3	Q8N112
	LSMEM2	ENST00000948603.1		c.355G>C	p.Ala119Pro	missense	Exon 3 of 4	ENSP00000618662.1
	LSMEM2	ENST00000878856.1		c.334G>C	p.Ala112Pro	missense	Exon 3 of 4	ENSP00000548915.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.3
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.31		Loss of catalytic residue at A113 (P = 0.1037)
MVP		0.040
MPC		0.60
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.85
gMVP		0.59
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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

dbSNP: rs147348613; hg19: chr3-50324269;