Variant 17-18487709-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000328114.11(LGALS9C):c.396C>A(p.Asp132Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,557,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000078 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LGALS9C
ENST00000328114.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.30

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.39117005).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9C	NM_001040078.3 linkuse as main transcript	c.396C>A	p.Asp132Glu	missense_variant	4/11	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.396C>A	p.Asp132Glu	missense_variant	4/11	1	NM_001040078.3	ENSP00000329932	P2

Frequencies

GnomAD3 genomes

AF:

0.0000783

AC:

AN:

140546

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000709

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:

0.00

GnomAD3 exomes

AF:

0.0000173

AC:

AN:

230628

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

124824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000306

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:

0.0000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1417316

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

704664

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000116

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:

0.0000111

Gnomad4 OTH exome

AF:

0.0000341

GnomAD4 genome

AF:

0.0000782

AC:

AN:

140630

Hom.:

Cov.:

AF XY:

0.0000730

AC XY:

AN XY:

68456

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.000708

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:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000167

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

Mar 06, 2023

The c.396C>A (p.D132E) alteration is located in exon 4 (coding exon 4) of the LGALS9C gene. This alteration results from a C to A substitution at nucleotide position 396, causing the aspartic acid (D) at amino acid position 132 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.10

.;.;T;.;.

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.80

M_CAP

Benign

0.0039

MetaRNN

Benign

0.39

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

.;.;M;.;.

MutationTaster

Benign

0.89

D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.6

.;.;D;.;.

REVEL

Benign

0.082

Sift

Uncertain

0.0030

.;.;D;.;.

Sift4G

Uncertain

0.013

D;D;D;D;D

Polyphen

0.94

.;.;P;.;.

Vest4

0.48

MutPred

0.66

Loss of catalytic residue at N137 (P = 0.1736);Loss of catalytic residue at N137 (P = 0.1736);Loss of catalytic residue at N137 (P = 0.1736);Loss of catalytic residue at N137 (P = 0.1736);Loss of catalytic residue at N137 (P = 0.1736);

MVP

0.27

ClinPred

0.41

GERP RS

1.3

Varity_R

0.76

gMVP

0.20

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