17-27645868-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_009587.3(LGALS9):​c.584C>T​(p.Thr195Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LGALS9
NM_009587.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.128
Variant links:
Genes affected
LGALS9 (HGNC:6570): (galectin 9) The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The protein encoded by this gene is an S-type lectin. It is overexpressed in Hodgkin's disease tissue and might participate in the interaction between the H&RS cells with their surrounding cells and might thus play a role in the pathogenesis of this disease and/or its associated immunodeficiency. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11327356).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LGALS9NM_009587.3 linkc.584C>T p.Thr195Ile missense_variant Exon 7 of 11 ENST00000395473.7 NP_033665.1 O00182-1A0A024QZ55

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LGALS9ENST00000395473.7 linkc.584C>T p.Thr195Ile missense_variant Exon 7 of 11 1 NM_009587.3 ENSP00000378856.2 O00182-1

Frequencies

GnomAD3 genomes
Cov.:
28
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000138
AC:
2
AN:
1452332
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
722448
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
28

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.584C>T (p.T195I) alteration is located in exon 7 (coding exon 7) of the LGALS9 gene. This alteration results from a C to T substitution at nucleotide position 584, causing the threonine (T) at amino acid position 195 to be replaced by an isoleucine (I). 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
Uncertain
0.34
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;.;.;T;T
Eigen
Benign
-0.80
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.064
N
LIST_S2
Uncertain
0.86
D;D;D;T;D
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L;.;.;.;.
PrimateAI
Benign
0.44
T
PROVEAN
Uncertain
-3.5
D;D;D;.;.
REVEL
Benign
0.032
Sift
Benign
0.071
T;T;T;.;.
Sift4G
Benign
0.10
T;T;T;D;D
Polyphen
0.10
B;.;.;.;.
Vest4
0.41
MutPred
0.35
Loss of phosphorylation at T195 (P = 0.0287);.;.;.;.;
MVP
0.51
MPC
1.5
ClinPred
0.42
T
GERP RS
-0.14
Varity_R
0.058
gMVP
0.23

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-25972894; API