Genetic Variant NM_018385.3:c.1880C>G (chr3-194642165-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_018385.3(LSG1):c.1880C>G(p.Ala627Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

LSG1
NM_018385.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.862

Variant links:

Genes affected

LSG1 (HGNC:25652): (large 60S subunit nuclear export GTPase 1) This gene encodes a protein related to the yeast large subunit GTPase 1. The encoded protein is necessary for cell viability and may localize in the endoplasmic reticulum, nucleus and cytoplasm.[provided by RefSeq, Feb 2009]

LSG1 links:

TMEM44-AS2 (HGNC:41082): (TMEM44 antisense RNA 2)

TMEM44-AS2 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=0.021331519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LSG1	NM_018385.3 link	c.1880C>G	p.Ala627Gly	missense_variant	Exon 14 of 14	ENST00000265245.10	NP_060855.2	Q9H089
TMEM44-AS2	NR_186047.1 link	n.241-2510G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LSG1	ENST00000265245.10 link	c.1880C>G	p.Ala627Gly	missense_variant	Exon 14 of 14	1	NM_018385.3	ENSP00000265245.5	Q9H089
LSG1	ENST00000475763.5 link	n.538C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3
TMEM44-AS2	ENST00000447139.2 link	n.265-2510G>C		intron_variant	Intron 1 of 1	2
LSG1	ENST00000460584.1 link	n.*8C>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000436

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251466

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000119

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.000436

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.17

DANN

Benign

0.38

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.14

M_CAP

Benign

0.0035

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.89

REVEL

Benign

0.043

Sift

Benign

0.41

Sift4G

Benign

0.37

Polyphen

0.012

Vest4

0.048

MVP

0.014

MPC

0.10

ClinPred

0.0064

GERP RS

-2.8

Varity_R

0.092

gMVP

0.16

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over