Genetic Variant NM_009587.3:c.13G>A (chr17-27631278-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

40 publications found

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:

ENSG00000266728 (HGNC:):

ENSG00000266728 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LGALS9	NM_009587.3 link	c.13G>A	p.Gly5Ser	missense_variant	Exon 1 of 11	ENST00000395473.7	NP_033665.1	O00182-1A0A024QZ55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS9	ENST00000395473.7 link	c.13G>A	p.Gly5Ser	missense_variant	Exon 1 of 11	1	NM_009587.3	ENSP00000378856.2		O00182-1
ENSG00000266728	ENST00000584605.5 link	n.*24-6985G>A		intron_variant	Intron 1 of 2	2		ENSP00000463557.1		J3QLI3

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

GnomAD2 exomes

AF:

0.225

AC:

56663

AN:

251364

AF XY:

0.226

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 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

African (AFR)

AF:

0.121

AC:

4056

AN:

33474

American (AMR)

AF:

0.303

AC:

13533

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

6309

AN:

26130

East Asian (EAS)

AF:

0.279

AC:

11086

AN:

39694

South Asian (SAS)

AF:

0.252

AC:

21722

AN:

86248

European-Finnish (FIN)

AF:

0.189

AC:

10114

AN:

53404

Middle Eastern (MID)

AF:

0.186

AC:

1069

AN:

5762

European-Non Finnish (NFE)

AF:

0.214

AC:

237693

AN:

1111800

Other (OTH)

AF:

0.216

AC:

13018

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

15584

31168

46753

62337

77921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8320

16640

24960

33280

41600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.194

AC:

29467

AN:

152172

Hom.:

3029

Cov.:

AF XY:

0.193

AC XY:

14355

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.124

AC:

5131

AN:

41514

American (AMR)

AF:

0.265

AC:

4053

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

784

AN:

3468

East Asian (EAS)

AF:

0.246

AC:

1274

AN:

5170

South Asian (SAS)

AF:

0.253

AC:

1221

AN:

4828

European-Finnish (FIN)

AF:

0.190

AC:

2013

AN:

10590

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.212

AC:

14441

AN:

67996

Other (OTH)

AF:

0.214

AC:

453

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1195

2390

3584

4779

5974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.200

Hom.:

7932

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

(source)

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;.

PhyloP100

-3.7

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

PromoterAI

-0.083

Neutral

(source)

Varity_R

0.24

gMVP

0.43

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over