Variant 3-194642165-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000265245.10(LSG1):c.1880C>T(p.Ala627Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 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. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A627E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000076 ( 0 hom. )

Consequence

LSG1
ENST00000265245.10 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02425623).

BP6

Variant 3-194642165-G-A is Benign according to our data. Variant chr3-194642165-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2396462.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LSG1	NM_018385.3 linkuse as main transcript	c.1880C>T	p.Ala627Val	missense_variant	14/14	ENST00000265245.10	NP_060855.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LSG1	ENST00000265245.10 linkuse as main transcript	c.1880C>T	p.Ala627Val	missense_variant	14/14	1	NM_018385.3	ENSP00000265245	P1
TMEM44-AS2	ENST00000447139.2 linkuse as main transcript	n.265-2510G>A		intron_variant, non_coding_transcript_variant		2
LSG1	ENST00000475763.5 linkuse as main transcript	n.538C>T		non_coding_transcript_exon_variant	3/3	3
LSG1	ENST00000460584.1 linkuse as main transcript			downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000135

AC:

AN:

251466

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000527

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000759

AC:

111

AN:

1461812

Hom.:

Cov.:

AF XY:

0.0000949

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74172

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000128

Hom.:

Bravo

AF:

0.0000907

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.72

DANN

Benign

0.70

DEOGEN2

Benign

0.0029

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.15

M_CAP

Benign

0.0032

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.12

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.23

REVEL

Benign

0.014

Sift

Benign

0.40

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.023

MutPred

0.17

Loss of sheet (P = 0.0142);

MVP

0.014

MPC

0.10

ClinPred

0.012

GERP RS

-2.8

Varity_R

0.060

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over