Genetic Variant NM_001367292.2:c.17C>A (chr17-20467454-G-T) – 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>A(p.Ser6Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 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 0.0 ( 0 hom., cov: 7)

Exomes 𝑓: 0.0000024 ( 0 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=0.08428657).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9B	NM_001367292.2	MANE Select	c.17C>A	p.Ser6Tyr	missense	Exon 1 of 11	NP_001354221.1
	LGALS9B	NM_001042685.3		c.17C>A	p.Ser6Tyr	missense	Exon 1 of 11	NP_001036150.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LGALS9B	ENST00000423676.8	TSL:1 MANE Select	c.17C>A	p.Ser6Tyr	missense	Exon 1 of 11	ENSP00000388841.3
LGALS9B	ENST00000324290.5	TSL:5	c.17C>A	p.Ser6Tyr	missense	Exon 1 of 11	ENSP00000315564.5
LGALS9B	ENST00000578481.5	TSL:2	n.17C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000464627.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

49430

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000240

AC:

AN:

417400

Hom.:

Cov.:

AF XY:

0.00000473

AC XY:

AN XY:

211562

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6918

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:

0.0000323

AC:

AN:

30940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1376

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

289272

Other (OTH)

AF:

0.00

AC:

AN:

19878

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

49430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

22866

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:

0.00

AC:

AN:

27166

Other (OTH)

AF:

0.00

AC:

AN:

600

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.6

(source)

DANN

Benign

0.80

DEOGEN2

Benign

0.0058

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.73

M_CAP

Benign

0.0021

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

PhyloP100

-0.47

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.9

REVEL

Benign

0.015

Sift

Benign

0.15

Sift4G

Benign

0.95

Polyphen

0.12

Vest4

0.094

MutPred

0.24

Loss of glycosylation at S6 (P = 0.012)

MVP

0.030

ClinPred

0.089

GERP RS

-0.15

PromoterAI

0.026

Neutral

(source)

Varity_R

0.047

gMVP

0.16

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over