dbSNP rs4985834: 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:

Genome browser will be placed here

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 link	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 link	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 11		NP_001036150.1	Q3B8N2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LGALS9B	ENST00000423676.8 link	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 11	1	NM_001367292.2	ENSP00000388841.3	Q3B8N2-1
LGALS9B	ENST00000324290.5 link	c.17C>T	p.Ser6Phe	missense_variant	Exon 1 of 11	5		ENSP00000315564.5	Q3B8N2-2
LGALS9B	ENST00000578481.5 link	n.17C>T		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000464627.1	J3QSC5

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 v4.3

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

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0094

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.8

L;L

PhyloP100

-0.47

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.018

Sift

Benign

0.13

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.12

B;B

Vest4

0.14

MutPred

0.26

Loss of disorder (P = 0.0053);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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over