rs1562003451

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016571.3(LGSN):​c.456G>T​(p.Glu152Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LGSN
NM_016571.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

Publications

0 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08284989).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LGSNNM_016571.3 linkc.456G>T p.Glu152Asp missense_variant Exon 4 of 4 ENST00000370657.9 NP_057655.2 Q5TDP6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LGSNENST00000370657.9 linkc.456G>T p.Glu152Asp missense_variant Exon 4 of 4 1 NM_016571.3 ENSP00000359691.4 Q5TDP6-1
LGSNENST00000370658.9 linkc.456G>T p.Glu152Asp missense_variant Exon 4 of 5 1 ENSP00000359692.5 Q5TDP6-2
LGSNENST00000485906.6 linkc.456G>T p.Glu152Asp missense_variant Exon 4 of 5 3 ENSP00000431246.2 A0A0A0MTD2
LGSNENST00000622415.1 linkc.*181G>T 3_prime_UTR_variant Exon 5 of 5 2 ENSP00000479173.1 Q5TDP6-3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461884
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112008
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jun 22, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.456G>T (p.E152D) alteration is located in exon 4 (coding exon 4) of the LGSN gene. This alteration results from a G to T substitution at nucleotide position 456, causing the glutamic acid (E) at amino acid position 152 to be replaced by an aspartic acid (D). 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
0.11
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
4.7
DANN
Benign
0.046
DEOGEN2
Benign
0.0050
.;T;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.56
D
LIST_S2
Benign
0.78
T;T;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.083
T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
-2.3
N;.;N
PhyloP100
1.3
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
2.5
N;N;N
REVEL
Benign
0.15
Sift
Benign
1.0
T;T;T
Sift4G
Benign
1.0
T;.;T
Polyphen
0.27
B;.;B
Vest4
0.099
MutPred
0.57
Loss of catalytic residue at E152 (P = 0.1974);Loss of catalytic residue at E152 (P = 0.1974);Loss of catalytic residue at E152 (P = 0.1974);
MVP
0.15
MPC
0.013
ClinPred
0.12
T
GERP RS
2.5
Varity_R
0.056
gMVP
0.64
Mutation Taster
=98/2
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1562003451; hg19: chr6-63991000; API