chr6-63280818-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016571.3(LGSN):​c.733G>A​(p.Asp245Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,842 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 (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

LGSN
NM_016571.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13861015).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LGSNNM_016571.3 linkuse as main transcriptc.733G>A p.Asp245Asn missense_variant 4/4 ENST00000370657.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LGSNENST00000370657.9 linkuse as main transcriptc.733G>A p.Asp245Asn missense_variant 4/41 NM_016571.3 P1Q5TDP6-1
LGSNENST00000370658.9 linkuse as main transcriptc.529+204G>A intron_variant 1 Q5TDP6-2
LGSNENST00000622415.1 linkuse as main transcriptc.*458G>A 3_prime_UTR_variant 5/52 Q5TDP6-3
LGSNENST00000485906.6 linkuse as main transcriptc.529+204G>A intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152112
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251040
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135740
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000239
AC:
35
AN:
1461730
Hom.:
0
Cov.:
33
AF XY:
0.0000275
AC XY:
20
AN XY:
727160
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:
0.0000306
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152112
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

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 06, 2022The c.733G>A (p.D245N) 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 733, causing the aspartic acid (D) at amino acid position 245 to be replaced by an asparagine (N). 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
0.080
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
19
DANN
Benign
0.92
DEOGEN2
Benign
0.033
T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.58
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.025
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-0.72
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
0.96
D;D
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.25
Sift
Benign
0.27
T
Sift4G
Benign
0.37
T
Polyphen
0.0030
B
Vest4
0.17
MVP
0.56
MPC
0.014
ClinPred
0.059
T
GERP RS
3.7
Varity_R
0.10
gMVP
0.62

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: rs367925464; hg19: chr6-63990723; API