Variant rs3751093 details in Genebe, Genetics Data Aggregator

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

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]

LGALS9 links:

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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
LGALS9	NM_009587.3 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/11	ENST00000395473.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS9	ENST00000395473.7 linkuse as main transcript	c.13G>A	p.Gly5Ser	missense_variant	1/11	1	NM_009587.3	P4	O00182-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29465

AN:

152052

Hom.:

3028

Cov.:

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.:

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.:

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

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

LIST_S2

Benign

0.39

T;T;T;T

MetaRNN

Benign

0.0045

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.17

N;N;N;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.31

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over