Variant 17-18486088-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001040078.3(LGALS9C):c.286G>A(p.Gly96Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000517 in 1,159,614 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 16)

Exomes 𝑓: 0.0000052 ( 2 hom. )

Consequence

LGALS9C
NM_001040078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

Variant links:

Genes affected

LGALS9C (HGNC:33874): (galectin 9C) 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 telomeric gene. [provided by RefSeq, Jul 2008]

LGALS9C links:

LGALS9C (HGNC:):

LGALS9C links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9C	NM_001040078.3 linkuse as main transcript	c.286G>A	p.Gly96Arg	missense_variant	3/11	ENST00000328114.11	NP_001035167.2	Q6DKI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9C	ENST00000328114.11 linkuse as main transcript	c.286G>A	p.Gly96Arg	missense_variant	3/11	1	NM_001040078.3	ENSP00000329932.6		Q6DKI2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000193

AC:

AN:

207476

Hom.:

AF XY:

0.0000179

AC XY:

AN XY:

111846

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:

0.0000461

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000517

AC:

AN:

1159614

Hom.:

Cov.:

AF XY:

0.00000173

AC XY:

AN XY:

577760

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:

0.00000699

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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

Dec 27, 2023

The c.286G>A (p.G96R) alteration is located in exon 3 (coding exon 3) of the LGALS9C gene. This alteration results from a G to A substitution at nucleotide position 286, causing the glycine (G) at amino acid position 96 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

0.60

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Benign

0.79

DEOGEN2

Benign

0.17

.;.;T;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.58

D;D;D;D;D

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.5

.;.;M;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.4

.;.;D;.;.

REVEL

Benign

0.23

Sift

Uncertain

0.027

.;.;D;.;.

Sift4G

Uncertain

0.015

D;D;D;D;D

Polyphen

0.99

.;.;D;.;.

Vest4

0.75

MutPred

0.75

Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);Gain of solvent accessibility (P = 0.006);

MVP

0.14

ClinPred

0.95

GERP RS

3.0

Varity_R

0.62

gMVP

0.67

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