Variant NM_001367292.2:c.880A>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 NM_001367292.2(LGALS9B):c.880A>T(p.Ser294Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 13)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9B
NM_001367292.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.184

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=0.22627479).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 link	c.880A>T	p.Ser294Cys	missense_variant	Exon 10 of 11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 link	c.877A>T	p.Ser293Cys	missense_variant	Exon 10 of 11		NP_001036150.1	Q3B8N2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LGALS9B	ENST00000423676.8 link	c.880A>T	p.Ser294Cys	missense_variant	Exon 10 of 11	1	NM_001367292.2	ENSP00000388841.3	Q3B8N2-1
LGALS9B	ENST00000324290.5 link	c.877A>T	p.Ser293Cys	missense_variant	Exon 10 of 11	5		ENSP00000315564.5	Q3B8N2-2
LGALS9B	ENST00000578481.5 link	n.*680A>T		non_coding_transcript_exon_variant	Exon 9 of 10	2		ENSP00000464627.1	J3QSC5
LGALS9B	ENST00000578481.5 link	n.*680A>T		3_prime_UTR_variant	Exon 9 of 10	2		ENSP00000464627.1	J3QSC5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000418

AC:

AN:

239428

Hom.:

AF XY:

0.00000766

AC XY:

AN XY:

130618

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:

0.00000944

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000171

AC:

AN:

1458224

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725204

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:

0.0000216

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.877A>T (p.S293C) alteration is located in exon 10 (coding exon 10) of the LGALS9B gene. This alteration results from a A to T substitution at nucleotide position 877, causing the serine (S) at amino acid position 293 to be replaced by a cysteine (C). 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

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.44

REVEL

Benign

0.12

Sift4G

Benign

0.082

T;T

Polyphen

0.99

D;D

Vest4

0.40

MutPred

0.53

Loss of disorder (P = 8e-04);.;

MVP

0.040

ClinPred

0.23

GERP RS

-0.52

Varity_R

0.18

gMVP

0.32

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