Variant chr3-194648692-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000265245.10(LSG1):c.1532C>A(p.Thr511Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

LSG1
ENST00000265245.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28059512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSG1	NM_018385.3 linkuse as main transcript	c.1532C>A	p.Thr511Lys	missense_variant	11/14	ENST00000265245.10	NP_060855.2	Q9H089

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LSG1	ENST00000265245.10 linkuse as main transcript	c.1532C>A	p.Thr511Lys	missense_variant	11/14	1	NM_018385.3	ENSP00000265245.5	Q9H089
LSG1	ENST00000437613.1 linkuse as main transcript	c.680C>A	p.Thr227Lys	missense_variant	4/6	5		ENSP00000408264.1	H7C2X7
LSG1	ENST00000460584.1 linkuse as main transcript	n.328C>A		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251248

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727156

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000247

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

Feb 16, 2023

The c.1532C>A (p.T511K) alteration is located in exon 11 (coding exon 11) of the LSG1 gene. This alteration results from a C to A substitution at nucleotide position 1532, causing the threonine (T) at amino acid position 511 to be replaced by a lysine (K). 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

0.22

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.011

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.85

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.9

REVEL

Benign

0.13

Sift

Benign

0.069

Sift4G

Benign

0.20

Polyphen

0.67

Vest4

0.66

MutPred

0.47

Gain of glycosylation at Y513 (P = 0.0019);

MVP

0.23

MPC

0.13

ClinPred

0.12

GERP RS

4.9

Varity_R

0.075

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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