17-27631278-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_009587.3(LGALS9):​c.13G>A​(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,782 control chromosomes in the GnomAD database, including 38,482 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3029 hom., cov: 32)
Exomes 𝑓: 0.22 ( 35453 hom. )

Consequence

LGALS9
NM_009587.3 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.69
Variant links:
Genes affected
LGALS9 (HGNC:6570): (galectin 9) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The protein encoded by this gene is an S-type lectin. It is overexpressed in Hodgkin's disease tissue and might participate in the interaction between the H&RS cells with their surrounding cells and might thus play a role in the pathogenesis of this disease and/or its associated immunodeficiency. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0045009255).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LGALS9NM_009587.3 linkuse as main transcriptc.13G>A p.Gly5Ser missense_variant 1/11 ENST00000395473.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LGALS9ENST00000395473.7 linkuse as main transcriptc.13G>A p.Gly5Ser missense_variant 1/111 NM_009587.3 P4O00182-1

Frequencies

GnomAD3 genomes
AF:
0.194
AC:
29465
AN:
152052
Hom.:
3028
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.124
Gnomad AMI
AF:
0.0606
Gnomad AMR
AF:
0.265
Gnomad ASJ
AF:
0.226
Gnomad EAS
AF:
0.247
Gnomad SAS
AF:
0.254
Gnomad FIN
AF:
0.190
Gnomad MID
AF:
0.142
Gnomad NFE
AF:
0.212
Gnomad OTH
AF:
0.217
GnomAD3 exomes
AF:
0.225
AC:
56663
AN:
251364
Hom.:
6800
AF XY:
0.226
AC XY:
30669
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.121
Gnomad AMR exome
AF:
0.304
Gnomad ASJ exome
AF:
0.240
Gnomad EAS exome
AF:
0.253
Gnomad SAS exome
AF:
0.251
Gnomad FIN exome
AF:
0.189
Gnomad NFE exome
AF:
0.211
Gnomad OTH exome
AF:
0.219
GnomAD4 exome
AF:
0.218
AC:
318600
AN:
1461610
Hom.:
35453
Cov.:
33
AF XY:
0.219
AC XY:
158968
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.121
Gnomad4 AMR exome
AF:
0.303
Gnomad4 ASJ exome
AF:
0.241
Gnomad4 EAS exome
AF:
0.279
Gnomad4 SAS exome
AF:
0.252
Gnomad4 FIN exome
AF:
0.189
Gnomad4 NFE exome
AF:
0.214
Gnomad4 OTH exome
AF:
0.216
GnomAD4 genome
AF:
0.194
AC:
29467
AN:
152172
Hom.:
3029
Cov.:
32
AF XY:
0.193
AC XY:
14355
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.124
Gnomad4 AMR
AF:
0.265
Gnomad4 ASJ
AF:
0.226
Gnomad4 EAS
AF:
0.246
Gnomad4 SAS
AF:
0.253
Gnomad4 FIN
AF:
0.190
Gnomad4 NFE
AF:
0.212
Gnomad4 OTH
AF:
0.214
Alfa
AF:
0.197
Hom.:
2514
Bravo
AF:
0.197
TwinsUK
AF:
0.215
AC:
796
ALSPAC
AF:
0.216
AC:
831
ESP6500AA
AF:
0.129
AC:
568
ESP6500EA
AF:
0.210
AC:
1808
ExAC
AF:
0.220
AC:
26736
Asia WGS
AF:
0.230
AC:
799
AN:
3478
EpiCase
AF:
0.213
EpiControl
AF:
0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.85
T
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.0090
DANN
Benign
0.72
DEOGEN2
Benign
0.086
T;.;.;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.029
N
LIST_S2
Benign
0.39
T;T;T;T
MetaRNN
Benign
0.0045
T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.17
N;N;N;.
MutationTaster
Benign
1.0
P;P;P;P;P
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.62
N;N;N;.
REVEL
Benign
0.020
Sift
Benign
1.0
T;T;T;.
Sift4G
Benign
0.53
T;T;T;T
Polyphen
0.0
B;.;.;.
Vest4
0.042
MPC
0.28
ClinPred
0.0038
T
GERP RS
-5.4
Varity_R
0.24
gMVP
0.43

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs3751093; hg19: chr17-25958304; COSMIC: COSV56349194; COSMIC: COSV56349194; API