chr6-63280026-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016571.3(LGSN):āc.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
NM_016571.3 missense
Scores
5
4
10
Clinical Significance
Conservation
PhyloP100: 5.95
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 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 |
---|---|---|---|---|---|---|---|
LGSN | NM_016571.3 | c.1525A>G | p.Ile509Val | missense_variant | 4/4 | ENST00000370657.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LGSN | ENST00000370657.9 | c.1525A>G | p.Ile509Val | missense_variant | 4/4 | 1 | NM_016571.3 | P1 | |
LGSN | ENST00000370658.9 | c.*477A>G | 3_prime_UTR_variant | 5/5 | 1 | ||||
LGSN | ENST00000622415.1 | c.*1250A>G | 3_prime_UTR_variant | 5/5 | 2 | ||||
LGSN | ENST00000485906.6 | c.530-599A>G | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000485 AC: 7AN: 1444424Hom.: 0 Cov.: 29 AF XY: 0.00000279 AC XY: 2AN XY: 717766
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74384
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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 | Oct 18, 2021 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D
M_CAP
Benign
T
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MutPred
Gain of disorder (P = 0.1387);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at