Variant 17-20458311-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000423676.8(LGALS9B):c.205G>A(p.Gly69Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9B
ENST00000423676.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0430

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19461197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 linkuse as main transcript	c.205G>A	p.Gly69Arg	missense_variant	3/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 linkuse as main transcript	c.205G>A	p.Gly69Arg	missense_variant	3/11		NP_001036150.1	Q3B8N2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LGALS9B	ENST00000423676.8 linkuse as main transcript	c.205G>A	p.Gly69Arg	missense_variant	3/11	1	NM_001367292.2	ENSP00000388841.3	Q3B8N2-1
LGALS9B	ENST00000324290.5 linkuse as main transcript	c.205G>A	p.Gly69Arg	missense_variant	3/11	5		ENSP00000315564.5	Q3B8N2-2
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*5G>A		non_coding_transcript_exon_variant	2/10	2		ENSP00000464627.1	J3QSC5
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*5G>A		3_prime_UTR_variant	2/10	2		ENSP00000464627.1	J3QSC5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151964

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

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

GnomAD3 exomes

AF:

0.0000318

AC:

AN:

251230

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000178

AC:

AN:

1461720

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000395

AC:

AN:

151964

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2023

The c.205G>A (p.G69R) alteration is located in exon 3 (coding exon 3) of the LGALS9B gene. This alteration results from a G to A substitution at nucleotide position 205, causing the glycine (G) at amino acid position 69 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.9

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-6.2

D;D

REVEL

Benign

0.050

Sift

Benign

0.041

D;D

Sift4G

Benign

0.092

T;T

Polyphen

1.0

D;D

Vest4

0.26

MutPred

0.44

Gain of MoRF binding (P = 0.0432);Gain of MoRF binding (P = 0.0432);

MVP

0.088

ClinPred

0.69

GERP RS

1.9

Varity_R

0.29

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over