Variant 3-50286485-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153215.3(LSMEM2):c.73A>G(p.Met25Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000442 in 1,606,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

LSMEM2
NM_153215.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0660

Variant links:

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]

LSMEM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031209737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LSMEM2	NM_153215.3 linkuse as main transcript	c.73A>G	p.Met25Val	missense_variant	2/4	ENST00000316436.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LSMEM2	ENST00000316436.4 linkuse as main transcript	c.73A>G	p.Met25Val	missense_variant	2/4	1	NM_153215.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000507

AC:

AN:

236460

Hom.:

AF XY:

0.0000389

AC XY:

AN XY:

128606

show subpopulations

Gnomad AFR exome

AF:

0.0000690

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000376

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000440

AC:

AN:

1454226

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

722844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000160

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000460

Gnomad4 OTH exome

AF:

0.0000999

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000718

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

The c.73A>G (p.M25V) alteration is located in exon 2 (coding exon 2) of the LSMEM2 gene. This alteration results from a A to G substitution at nucleotide position 73, causing the methionine (M) at amino acid position 25 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.16

DANN

Benign

0.42

DEOGEN2

Benign

0.026

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.30

M_CAP

Benign

0.0010

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.14

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.0

REVEL

Benign

0.053

Sift

Benign

0.56

Sift4G

Benign

0.88

Polyphen

0.0

Vest4

0.11

MutPred

0.10

Gain of glycosylation at S28 (P = 0.0351);

MVP

0.014

MPC

0.11

ClinPred

0.024

GERP RS

0.36

Varity_R

0.051

gMVP

0.072

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over