6-63280340-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000370657.9(LGSN):​c.1211G>A​(p.Arg404Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,614,158 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 0.00025 ( 2 hom. )

Consequence

LGSN
ENST00000370657.9 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.046799988).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LGSNNM_016571.3 linkuse as main transcriptc.1211G>A p.Arg404Gln missense_variant 4/4 ENST00000370657.9 NP_057655.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LGSNENST00000370657.9 linkuse as main transcriptc.1211G>A p.Arg404Gln missense_variant 4/41 NM_016571.3 ENSP00000359691 P1Q5TDP6-1
LGSNENST00000370658.9 linkuse as main transcriptc.*163G>A 3_prime_UTR_variant 5/51 ENSP00000359692 Q5TDP6-2
LGSNENST00000622415.1 linkuse as main transcriptc.*936G>A 3_prime_UTR_variant 5/52 ENSP00000479173 Q5TDP6-3
LGSNENST00000485906.6 linkuse as main transcriptc.529+682G>A intron_variant 3 ENSP00000431246

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152164
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.000250
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000279
AC:
70
AN:
251218
Hom.:
1
AF XY:
0.000309
AC XY:
42
AN XY:
135852
show subpopulations
Gnomad AFR exome
AF:
0.0000620
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000915
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000238
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000248
AC:
363
AN:
1461876
Hom.:
2
Cov.:
33
AF XY:
0.000276
AC XY:
201
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000402
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00105
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000218
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000144
AC:
22
AN:
152282
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000214
Hom.:
0
Bravo
AF:
0.000132
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000239
AC:
29
EpiCase
AF:
0.000218
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 submitterclinical testingAmbry GeneticsFeb 16, 2023The c.1211G>A (p.R404Q) alteration is located in exon 4 (coding exon 4) of the LGSN gene. This alteration results from a G to A substitution at nucleotide position 1211, causing the arginine (R) at amino acid position 404 to be replaced by a glutamine (Q). 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
0.064
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
17
DANN
Benign
0.92
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.047
T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.27
Sift
Benign
0.31
T
Sift4G
Benign
0.39
T
Polyphen
0.059
B
Vest4
0.077
MVP
0.63
MPC
0.013
ClinPred
0.043
T
GERP RS
2.8
Varity_R
0.055
gMVP
0.47

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.

Other links and lift over

dbSNP: rs199883532; hg19: chr6-63990245; API