Variant 17-18492745-C-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.810C>A(p.Asn270Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,506,144 control chromosomes in the GnomAD database, including 16 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000090 ( 3 hom., cov: 24)

Exomes 𝑓: 0.00013 ( 13 hom. )

Consequence

LGALS9C
NM_001040078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.744

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.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9C	NM_001040078.3 link	c.810C>A	p.Asn270Lys	missense_variant	10/11	ENST00000328114.11	NP_001035167.2	Q6DKI2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9C	ENST00000328114.11 link	c.810C>A	p.Asn270Lys	missense_variant	10/11	1	NM_001040078.3	ENSP00000329932.6		Q6DKI2

Frequencies

GnomAD3 genomes

AF:

0.0000900

AC:

AN:

133306

Hom.:

Cov.:

show subpopulations

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:

0.000463

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000143

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000188

AC:

AN:

233442

Hom.:

AF XY:

0.000190

AC XY:

AN XY:

126006

show subpopulations

Gnomad AFR exome

AF:

0.000125

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:

0.000505

Gnomad NFE exome

AF:

0.000295

Gnomad OTH exome

AF:

0.000352

GnomAD4 exome

AF:

0.000130

AC:

179

AN:

1372714

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

683512

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000661

Gnomad4 NFE exome

AF:

0.000133

Gnomad4 OTH exome

AF:

0.000105

GnomAD4 genome

AF:

0.0000899

AC:

AN:

133430

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

65304

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:

0.000463

Gnomad4 NFE

AF:

0.000143

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000293

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

Dec 03, 2024

The c.810C>A (p.N270K) alteration is located in exon 10 (coding exon 10) of the LGALS9C gene. This alteration results from a C to A substitution at nucleotide position 810, causing the asparagine (N) at amino acid position 270 to be replaced by a lysine (K). 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

0.96

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

0.13

Eigen_PC

Benign

-0.037

FATHMM_MKL

Benign

0.66

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-4.9

D;.

REVEL

Benign

0.29

Sift

Benign

0.062

T;.

Sift4G

Uncertain

0.028

D;D

Polyphen

1.0

D;.

Vest4

0.89

MutPred

0.86

Gain of methylation at N270 (P = 0.0236);.;

MVP

0.21

ClinPred

0.37

GERP RS

1.3

Varity_R

0.46

gMVP

0.59

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