Variant chr3-194642147-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000265245.10(LSG1):c.1898C>T(p.Ala633Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,613,566 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

LSG1
ENST00000265245.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.149

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:

LSG1 (HGNC:):

LSG1 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=0.023689449).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSG1	NM_018385.3 linkuse as main transcript	c.1898C>T	p.Ala633Val	missense_variant	14/14	ENST00000265245.10	NP_060855.2	Q9H089
TMEM44-AS2	NR_186047.1 linkuse as main transcript	n.241-2528G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LSG1	ENST00000265245.10 linkuse as main transcript	c.1898C>T	p.Ala633Val	missense_variant	14/14	1	NM_018385.3	ENSP00000265245.5	Q9H089
LSG1	ENST00000475763.5 linkuse as main transcript	n.556C>T		non_coding_transcript_exon_variant	3/3	3
TMEM44-AS2	ENST00000447139.2 linkuse as main transcript	n.265-2528G>A		intron_variant		2
LSG1	ENST00000460584.1 linkuse as main transcript	n.*26C>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

151760

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000291

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000175

AC:

AN:

251434

Hom.:

AF XY:

0.000191

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000137

AC:

200

AN:

1461690

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

113

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000244

AC:

AN:

151876

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000264

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

Sep 17, 2021

The c.1898C>T (p.A633V) alteration is located in exon 14 (coding exon 14) of the LSG1 gene. This alteration results from a C to T substitution at nucleotide position 1898, causing the alanine (A) at amino acid position 633 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

0.073

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.4

DANN

Benign

0.93

DEOGEN2

Benign

0.0036

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.48

M_CAP

Benign

0.0056

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.73

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.43

REVEL

Benign

0.016

Sift

Benign

0.36

Sift4G

Benign

0.48

Polyphen

0.012

Vest4

0.030

MVP

0.030

MPC

0.10

ClinPred

0.0086

GERP RS

0.89

Varity_R

0.083

gMVP

0.15

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over