Variant 6-63280226-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000370657.9(LGSN):c.1325A>G(p.Asp442Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00245 in 1,614,204 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

LGSN
ENST00000370657.9 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.822

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00319916).

BP6

Variant 6-63280226-T-C is Benign according to our data. Variant chr6-63280226-T-C is described in ClinVar as [Benign]. Clinvar id is 783466.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0135 (2061/152314) while in subpopulation AFR AF= 0.0466 (1935/41562). AF 95% confidence interval is 0.0448. There are 47 homozygotes in gnomad4. There are 981 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGSN	NM_016571.3 linkuse as main transcript	c.1325A>G	p.Asp442Gly	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.1325A>G	p.Asp442Gly	missense_variant	4/4	1	NM_016571.3	ENSP00000359691	P1	Q5TDP6-1
LGSN	ENST00000370658.9 linkuse as main transcript	c.*277A>G		3_prime_UTR_variant	5/5	1		ENSP00000359692		Q5TDP6-2
LGSN	ENST00000622415.1 linkuse as main transcript	c.*1050A>G		3_prime_UTR_variant	5/5	2		ENSP00000479173		Q5TDP6-3
LGSN	ENST00000485906.6 linkuse as main transcript	c.529+796A>G		intron_variant		3		ENSP00000431246

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2055

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0465

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00346

AC:

870

AN:

251422

Hom.:

AF XY:

0.00254

AC XY:

345

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.0458

Gnomad AMR exome

AF:

0.00286

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00129

AC:

1888

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

778

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0451

Gnomad4 AMR exome

AF:

0.00282

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.00300

GnomAD4 genome

AF:

0.0135

AC:

2061

AN:

152314

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

981

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0466

Gnomad4 AMR

AF:

0.00654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00606

Hom.:

Bravo

AF:

0.0155

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0429

AC:

189

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00404

AC:

490

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.0

DANN

Benign

0.61

DEOGEN2

Benign

0.031

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.72

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.77

REVEL

Benign

0.14

Sift

Benign

0.34

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.12

MVP

0.51

MPC

0.013

ClinPred

0.0015

GERP RS

2.2

Varity_R

0.068

gMVP

0.34

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