Variant 17-18486106-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000328114.11(LGALS9C):c.304T>G(p.Cys102Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 4 hom., cov: 15)

Exomes 𝑓: 0.000052 ( 14 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9C
ENST00000328114.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.03

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028937548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9C	NM_001040078.3 linkuse as main transcript	c.304T>G	p.Cys102Gly	missense_variant	3/11	ENST00000328114.11	NP_001035167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9C	ENST00000328114.11 linkuse as main transcript	c.304T>G	p.Cys102Gly	missense_variant	3/11	1	NM_001040078.3	ENSP00000329932	P2

Frequencies

GnomAD3 genomes

AF:

0.000344

AC:

AN:

110404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000355

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:

0.00

Gnomad OTH

AF:

0.000691

GnomAD3 exomes

AF:

0.0000791

AC:

AN:

176942

Hom.:

AF XY:

0.0000423

AC XY:

AN XY:

94564

show subpopulations

Gnomad AFR exome

AF:

0.00102

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000521

AC:

AN:

1152000

Hom.:

Cov.:

AF XY:

0.0000470

AC XY:

AN XY:

573962

show subpopulations

Gnomad4 AFR exome

AF:

0.00190

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:

0.00

Gnomad4 OTH exome

AF:

0.0000411

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000344

AC:

AN:

110516

Hom.:

Cov.:

AF XY:

0.000299

AC XY:

AN XY:

53588

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.000355

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:

0.000681

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.000159

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 11, 2024

The c.304T>G (p.C102G) alteration is located in exon 3 (coding exon 3) of the LGALS9C gene. This alteration results from a T to G substitution at nucleotide position 304, causing the cysteine (C) at amino acid position 102 to be replaced by a glycine (G). 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

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.11

.;.;T;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.057

M_CAP

Benign

0.0053

MetaRNN

Benign

0.029

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.5

.;.;M;.;.

MutationTaster

Benign

0.92

N;N;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.5

.;.;D;.;.

REVEL

Benign

0.13

Sift

Benign

0.35

.;.;T;.;.

Sift4G

Uncertain

0.042

D;T;T;T;T

Polyphen

0.30

.;.;B;.;.

Vest4

0.41

MVP

0.15

ClinPred

0.15

GERP RS

0.082

Varity_R

0.70

gMVP

0.51

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