NM_153215.3:c.19G>T

Variant names:

• chr3-50279132-G-T
• rs1425217757
• NM_153215.3:c.19G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153215.3(LSMEM2):​c.19G>T​(p.Asp7Tyr) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. 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. D7N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LSMEM2 NM_153215.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1183089).

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.19G>T	p.Asp7Tyr	missense	Exon 1 of 4	NP_694947.1	Q8N112
	LSMEM2	NM_001304385.2		c.19G>T	p.Asp7Tyr	missense	Exon 1 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.19G>T	p.Asp7Tyr	missense	Exon 1 of 4	ENSP00000315081.3	Q8N112
	LSMEM2	ENST00000948603.1		c.19G>T	p.Asp7Tyr	missense	Exon 1 of 4	ENSP00000618662.1
	LSMEM2	ENST00000878856.1		c.19G>T	p.Asp7Tyr	missense	Exon 1 of 4	ENSP00000548915.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.8
DANN	Benign	0.68
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.057
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.035
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.059	T
Polyphen		0.83	P
Vest4		0.17
MutPred		0.17		Gain of catalytic residue at D7 (P = 0.001)
MVP		0.030
MPC		0.42
ClinPred		0.44	T
GERP RS		1.4
PromoterAI		-0.051	Neutral
Varity_R		0.11
gMVP		0.12
Mutation Taster		=90/10	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

dbSNP: rs1425217757; hg19: chr3-50316563;