Genetic Variant LGALS9:p.Pro189Gln (chr17-27645339-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_009587.3(LGALS9):c.566C>A(p.Pro189Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P189L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LGALS9
NM_009587.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.286

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050889462).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_009587.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGALS9	NM_009587.3	MANE Select	c.566C>A	p.Pro189Gln	missense	Exon 6 of 11	NP_033665.1	O00182-1
LGALS9	NM_002308.4		c.470C>A	p.Pro157Gln	missense	Exon 5 of 10	NP_002299.2	O00182-2
LGALS9	NM_001330163.2		c.470C>A	p.Pro157Gln	missense	Exon 5 of 9	NP_001317092.1	O00182-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGALS9	ENST00000395473.7	TSL:1 MANE Select	c.566C>A	p.Pro189Gln	missense	Exon 6 of 11	ENSP00000378856.2	O00182-1
LGALS9	ENST00000302228.9	TSL:1	c.470C>A	p.Pro157Gln	missense	Exon 5 of 10	ENSP00000306228.5	O00182-2
LGALS9	ENST00000481514.5	TSL:1	n.1275C>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111822

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.62

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.18

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.39

M_CAP

Benign

0.00097

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.29

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.5

REVEL

Benign

0.0090

Sift

Benign

0.25

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.14

MutPred

0.17

Gain of MoRF binding (P = 0.0737)

MVP

0.13

MPC

1.2

ClinPred

0.093

GERP RS

-2.4

Varity_R

0.031

gMVP

0.13

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over