chr6-63280206-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016571.3(LGSN):ā€‹c.1345C>Gā€‹(p.Gln449Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00016 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (ā˜…).

Frequency

Genomes: š‘“ 0.00014 ( 0 hom., cov: 32)
Exomes š‘“: 0.00016 ( 0 hom. )

Consequence

LGSN
NM_016571.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.042158186).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LGSNNM_016571.3 linkuse as main transcriptc.1345C>G p.Gln449Glu missense_variant 4/4 ENST00000370657.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LGSNENST00000370657.9 linkuse as main transcriptc.1345C>G p.Gln449Glu missense_variant 4/41 NM_016571.3 P1Q5TDP6-1
LGSNENST00000370658.9 linkuse as main transcriptc.*297C>G 3_prime_UTR_variant 5/51 Q5TDP6-2
LGSNENST00000622415.1 linkuse as main transcriptc.*1070C>G 3_prime_UTR_variant 5/52 Q5TDP6-3
LGSNENST00000485906.6 linkuse as main transcriptc.530-779C>G intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000195
AC:
49
AN:
251410
Hom.:
0
AF XY:
0.000221
AC XY:
30
AN XY:
135874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000686
Gnomad FIN exome
AF:
0.000370
Gnomad NFE exome
AF:
0.000132
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000163
AC:
238
AN:
1461858
Hom.:
0
Cov.:
33
AF XY:
0.000180
AC XY:
131
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000556
Gnomad4 FIN exome
AF:
0.000618
Gnomad4 NFE exome
AF:
0.000129
Gnomad4 OTH exome
AF:
0.0000828
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.000202
AC XY:
15
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000831
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000173
AC:
21
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000119

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 GeneticsDec 11, 2023The c.1345C>G (p.Q449E) alteration is located in exon 4 (coding exon 4) of the LGSN gene. This alteration results from a C to G substitution at nucleotide position 1345, causing the glutamine (Q) at amino acid position 449 to be replaced by a glutamic acid (E). 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
0.060
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
5.8
DANN
Benign
0.25
DEOGEN2
Benign
0.012
T
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.51
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.52
T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.042
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
D;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
0.26
N
REVEL
Benign
0.21
Sift
Benign
0.72
T
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.10
MVP
0.57
MPC
0.013
ClinPred
0.051
T
GERP RS
5.1
Varity_R
0.12
gMVP
0.19

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: rs201490688; hg19: chr6-63990111; API