Variant 6-63280206-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000370657.9(LGSN):c.1345C>G(p.Gln449Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

LGSN
ENST00000370657.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

LGSN (HGNC:21016): (lengsin, lens protein with glutamine synthetase domain) This gene encodes a protein with similarity to the GS I members of the glutamine synthetase superfamily. The encoded protein is referred to as a pseudo-glutamine synthetase because it has no glutamine synthesis activity and may function as a chaperone protein. This protein is localized to the lens and may be associated with cataract disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

LGSN 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=0.042158186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGSN	NM_016571.3 linkuse as main transcript	c.1345C>G	p.Gln449Glu	missense_variant	4/4	ENST00000370657.9	NP_057655.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGSN	ENST00000370657.9 linkuse as main transcript	c.1345C>G	p.Gln449Glu	missense_variant	4/4	1	NM_016571.3	ENSP00000359691	P1	Q5TDP6-1
LGSN	ENST00000370658.9 linkuse as main transcript	c.*297C>G		3_prime_UTR_variant	5/5	1		ENSP00000359692		Q5TDP6-2
LGSN	ENST00000622415.1 linkuse as main transcript	c.*1070C>G		3_prime_UTR_variant	5/5	2		ENSP00000479173		Q5TDP6-3
LGSN	ENST00000485906.6 linkuse as main transcript	c.530-779C>G		intron_variant		3		ENSP00000431246

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

251410

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000686

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000163

AC:

238

AN:

1461858

Hom.:

Cov.:

AF XY:

0.000180

AC XY:

131

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000556

Gnomad4 FIN exome

AF:

0.000618

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000138

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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 11, 2023

The c.1345C>G (p.Q449E) alteration is located in exon 4 (coding exon 4) of the LGSN gene. This alteration results from a C to G substitution at nucleotide position 1345, causing the glutamine (Q) at amino acid position 449 to be replaced by a glutamic acid (E). 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

0.060

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.40

CADD

Benign

5.8

DANN

Benign

0.25

DEOGEN2

Benign

0.012

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.51

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.52

M_CAP

Benign

0.021

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.26

REVEL

Benign

0.21

Sift

Benign

0.72

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.10

MVP

0.57

MPC

0.013

ClinPred

0.051

GERP RS

5.1

Varity_R

0.12

gMVP

0.19

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