Variant 17-20455343-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001367292.2(LGALS9B):c.500C>G(p.Pro167Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,229,148 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000024 ( 1 hom., cov: 19)

Exomes 𝑓: 0.000028 ( 11 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9B
NM_001367292.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.594

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0765942).

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 linkuse as main transcript	c.500C>G	p.Pro167Arg	missense_variant	5/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 linkuse as main transcript	c.500C>G	p.Pro167Arg	missense_variant	5/11		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.500C>G	p.Pro167Arg	missense_variant	5/11	1	NM_001367292.2	ENSP00000388841.3	Q3B8N2-1
LGALS9B	ENST00000324290.5 linkuse as main transcript	c.500C>G	p.Pro167Arg	missense_variant	5/11	5		ENSP00000315564.5	Q3B8N2-2
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*300C>G		non_coding_transcript_exon_variant	4/10	2		ENSP00000464627.1	J3QSC5
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*300C>G		3_prime_UTR_variant	4/10	2		ENSP00000464627.1	J3QSC5

Frequencies

GnomAD3 genomes

AF:

0.0000237

AC:

AN:

126494

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:

0.0000558

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000704

AC:

AN:

213180

Hom.:

AF XY:

0.0000609

AC XY:

AN XY:

115036

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:

0.000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000285

AC:

AN:

1229148

Hom.:

Cov.:

AF XY:

0.0000359

AC XY:

AN XY:

612852

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:

0.0000360

Gnomad4 OTH exome

AF:

0.0000390

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000237

AC:

AN:

126494

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

61136

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:

0.0000558

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000112

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 30, 2024

The c.500C>G (p.P167R) alteration is located in exon 5 (coding exon 5) of the LGALS9B gene. This alteration results from a C to G substitution at nucleotide position 500, causing the proline (P) at amino acid position 167 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

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.34

N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.4

N;N

REVEL

Benign

0.053

Sift

Benign

0.085

T;T

Sift4G

Benign

0.097

T;T

Polyphen

0.94

P;P

Vest4

0.21

MVP

0.076

ClinPred

0.12

GERP RS

1.0

Varity_R

0.096

gMVP

0.083

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