Variant 17-20451518-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367292.2(LGALS9B):c.887C>T(p.Pro296Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,455,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000070 ( 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: 0.259

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065199256).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2 linkuse as main transcript	c.887C>T	p.Pro296Leu	missense_variant	10/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3 linkuse as main transcript	c.884C>T	p.Pro295Leu	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.887C>T	p.Pro296Leu	missense_variant	10/11	1	NM_001367292.2	ENSP00000388841.3	Q3B8N2-1
LGALS9B	ENST00000324290.5 linkuse as main transcript	c.884C>T	p.Pro295Leu	missense_variant	10/11	5		ENSP00000315564.5	Q3B8N2-2
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*687C>T		non_coding_transcript_exon_variant	9/10	2		ENSP00000464627.1	J3QSC5
LGALS9B	ENST00000578481.5 linkuse as main transcript	n.*687C>T		3_prime_UTR_variant	9/10	2		ENSP00000464627.1	J3QSC5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

96082

Hom.:

Cov.:

FAILED QC

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:

0.00435

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000843

GnomAD3 exomes

AF:

0.0000341

AC:

AN:

234454

Hom.:

AF XY:

0.0000469

AC XY:

AN XY:

127974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000583

Gnomad OTH exome

AF:

0.000175

GnomAD4 exome

AF:

0.0000701

AC:

102

AN:

1455722

Hom.:

Cov.:

AF XY:

0.0000635

AC XY:

AN XY:

723874

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000695

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000208

AC:

AN:

96156

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

45418

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:

0.00

Gnomad4 OTH

AF:

0.000831

Alfa

AF:

0.0000434

Hom.:

ExAC

AF:

0.0000248

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

Nov 15, 2021

The c.884C>T (p.P295L) alteration is located in exon 10 (coding exon 10) of the LGALS9B gene. This alteration results from a C to T substitution at nucleotide position 884, causing the proline (P) at amino acid position 295 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0032

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.46

REVEL

Benign

0.058

Sift4G

Benign

0.085

T;T

Polyphen

0.12

B;B

Vest4

0.16

MutPred

0.55

Loss of disorder (P = 0.0213);.;

MVP

0.081

ClinPred

0.033

GERP RS

-0.44

Varity_R

0.10

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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