Variant chr17-20451593-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001367292.2(LGALS9B):c.812C>G(p.Pro271Arg) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000092 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9B
NM_001367292.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.68

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:

LGALS9B (HGNC:):

LGALS9B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.963

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 linkuse as main transcript	c.812C>G	p.Pro271Arg	missense_variant	10/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 linkuse as main transcript	c.809C>G	p.Pro270Arg	missense_variant	10/11		NP_001036150.1	Q3B8N2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9B	ENST00000423676.8 linkuse as main transcript	c.812C>G	p.Pro271Arg	missense_variant	10/11	1	NM_001367292.2	ENSP00000388841.3		Q3B8N2-1

Frequencies

GnomAD3 genomes

AF:

0.00000737

AC:

AN:

135634

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:

0.0000164

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250574

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135536

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000796

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000924

AC:

135

AN:

1461176

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

726908

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000737

AC:

AN:

135634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000164

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000412

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

Jun 02, 2023

The c.809C>G (p.P270R) alteration is located in exon 10 (coding exon 10) of the LGALS9B gene. This alteration results from a C to G substitution at nucleotide position 809, causing the proline (P) at amino acid position 270 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

Pathogenic

0.97

BayesDel_addAF

Benign

-0.0024

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.0042

MetaRNN

Pathogenic

0.96

D;D

MetaSVM

Uncertain

0.31

MutationAssessor

Pathogenic

4.4

H;.

PrimateAI

Uncertain

0.67

REVEL

Pathogenic

0.73

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.92

MutPred

0.85

Gain of MoRF binding (P = 0.0648);.;

MVP

0.25

ClinPred

0.99

GERP RS

2.0

Varity_R

0.88

gMVP

0.70

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

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