Genetic Variant LGALS9B:p.Ser6Phe (chr17-20467454-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001367292.2(LGALS9B):c.17C>T(p.Ser6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. S6C) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 7)

Exomes 𝑓: 0.000019 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9B
NM_001367292.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.471

Publications

14 publications found

Variant links:

Genes affected

LGALS9B (HGNC:24842): (galectin 9B) This gene was initially thought to represent a pseudogene of galectin 9; however, this transcript has good exon-intron structure and encodes a predicted protein of the same size as and highly similar to galectin 9. This gene is one of two similar loci on chromosome 17p similar to galectin 9 and now thought to be protein-encoding. This gene is the more centromeric gene. [provided by RefSeq, Jul 2008]

LGALS9B links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.078609526).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367292.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9B	NM_001367292.2	MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 11	NP_001354221.1	Q3B8N2-1
	LGALS9B	NM_001042685.3		c.17C>T	p.Ser6Phe	missense	Exon 1 of 11	NP_001036150.1	Q3B8N2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGALS9B	ENST00000423676.8	TSL:1 MANE Select	c.17C>T	p.Ser6Phe	missense	Exon 1 of 11	ENSP00000388841.3	Q3B8N2-1
LGALS9B	ENST00000324290.5	TSL:5	c.17C>T	p.Ser6Phe	missense	Exon 1 of 11	ENSP00000315564.5	Q3B8N2-2
LGALS9B	ENST00000897463.1		c.17C>T	p.Ser6Phe	missense	Exon 1 of 10	ENSP00000567522.1

Frequencies

GnomAD3 genomes

AF:

0.0000405

AC:

AN:

49430

Hom.:

Cov.:

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:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000192

AC:

AN:

417406

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

211566

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

6920

American (AMR)

AF:

0.00

AC:

AN:

14850

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9634

East Asian (EAS)

AF:

0.00

AC:

AN:

20962

South Asian (SAS)

AF:

0.00

AC:

AN:

23570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1376

European-Non Finnish (NFE)

AF:

0.0000277

AC:

AN:

289274

Other (OTH)

AF:

0.00

AC:

AN:

19878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

AF:

0.0000405

AC:

AN:

49430

Hom.:

Cov.:

AF XY:

0.0000437

AC XY:

AN XY:

22866

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

8724

American (AMR)

AF:

0.00

AC:

AN:

4770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1510

East Asian (EAS)

AF:

0.00

AC:

AN:

2300

South Asian (SAS)

AF:

0.00

AC:

AN:

1018

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

118

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

27166

Other (OTH)

AF:

0.00

AC:

AN:

600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.800

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

3.0

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.76

M_CAP

Benign

0.0022

MetaRNN

Benign

0.079

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

PhyloP100

-0.47

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

REVEL

Benign

0.018

Sift

Benign

0.13

Sift4G

Benign

0.56

Polyphen

0.12

Vest4

0.14

MutPred

0.26

Loss of disorder (P = 0.0053)

MVP

0.030

ClinPred

0.12

GERP RS

-0.15

PromoterAI

0.021

Neutral

(source)

Varity_R

0.048

gMVP

0.13

Mutation Taster

=98/2

polymorphism

(source)

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

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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