chr6-63280026-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016571.3(LGSN):ā€‹c.1525A>Gā€‹(p.Ile509Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000626 in 1,596,664 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

LGSN
NM_016571.3 missense

Scores

5
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.95
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LGSNNM_016571.3 linkuse as main transcriptc.1525A>G p.Ile509Val missense_variant 4/4 ENST00000370657.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LGSNENST00000370657.9 linkuse as main transcriptc.1525A>G p.Ile509Val missense_variant 4/41 NM_016571.3 P1Q5TDP6-1
LGSNENST00000370658.9 linkuse as main transcriptc.*477A>G 3_prime_UTR_variant 5/51 Q5TDP6-2
LGSNENST00000622415.1 linkuse as main transcriptc.*1250A>G 3_prime_UTR_variant 5/52 Q5TDP6-3
LGSNENST00000485906.6 linkuse as main transcriptc.530-599A>G intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152240
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000485
AC:
7
AN:
1444424
Hom.:
0
Cov.:
29
AF XY:
0.00000279
AC XY:
2
AN XY:
717766
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000543
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152240
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 GeneticsOct 18, 2021The c.1525A>G (p.I509V) alteration is located in exon 4 (coding exon 4) of the LGSN gene. This alteration results from a A to G substitution at nucleotide position 1525, causing the isoleucine (I) at amino acid position 509 to be replaced by a valine (V). 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
0.14
BayesDel_addAF
Benign
-0.039
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.055
T
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.85
D
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.46
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.36
N
REVEL
Benign
0.15
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.99
D
Vest4
0.55
MutPred
0.46
Gain of disorder (P = 0.1387);
MVP
0.56
MPC
0.016
ClinPred
0.96
D
GERP RS
5.7
Varity_R
0.28
gMVP
0.45

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: rs977743643; hg19: chr6-63989931; API