Variant chr17-20451492-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000423676.8(LGALS9B):c.913C>G(p.Gln305Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000459 in 1,524,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., cov: 11)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

LGALS9B
ENST00000423676.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.75

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19350135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 linkuse as main transcript	c.913C>G	p.Gln305Glu	missense_variant	10/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 linkuse as main transcript	c.910C>G	p.Gln304Glu	missense_variant	10/11		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.913C>G	p.Gln305Glu	missense_variant	10/11	1	NM_001367292.2	ENSP00000388841.3	Q3B8N2-1
LGALS9B	ENST00000324290.5 linkuse as main transcript	c.910C>G	p.Gln304Glu	missense_variant	10/11	5		ENSP00000315564.5	Q3B8N2-2
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*713C>G		non_coding_transcript_exon_variant	9/10	2		ENSP00000464627.1	J3QSC5
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*713C>G		3_prime_UTR_variant	9/10	2		ENSP00000464627.1	J3QSC5

Frequencies

GnomAD3 genomes

AF:

0.0000115

AC:

AN:

87022

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:

0.000221

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:

0.0000343

AC:

AN:

204140

Hom.:

AF XY:

0.0000449

AC XY:

AN XY:

111280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000422

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000417

AC:

AN:

1437872

Hom.:

Cov.:

AF XY:

0.00000700

AC XY:

AN XY:

714606

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000115

AC:

AN:

87022

Hom.:

Cov.:

AF XY:

0.0000244

AC XY:

AN XY:

40964

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000221

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000499

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

May 17, 2023

The c.910C>G (p.Q304E) 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 910, causing the glutamine (Q) at amino acid position 304 to be replaced by a glutamic acid (E). 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

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

0.056

Eigen_PC

Benign

-0.058

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Benign

0.42

REVEL

Uncertain

0.29

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.98

D;D

Vest4

0.32

MutPred

0.62

Loss of MoRF binding (P = 0.1002);.;

MVP

0.030

ClinPred

0.38

GERP RS

2.0

Varity_R

0.43

gMVP

0.27

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