NM_009587.3:c.428C>T

Variant names:

• chr17-27642332-C-T
• NM_009587.3:c.428C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_009587.3(LGALS9):​c.428C>T​(p.Ser143Phe) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LGALS9 NM_009587.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.999
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1810523).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_009587.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9	NM_009587.3	MANE Select	c.428C>T	p.Ser143Phe	missense	Exon 4 of 11	NP_033665.1	O00182-1
	LGALS9	NM_002308.4		c.428C>T	p.Ser143Phe	missense	Exon 4 of 10	NP_002299.2	O00182-2
	LGALS9	NM_001330163.2		c.428C>T	p.Ser143Phe	missense	Exon 4 of 9	NP_001317092.1	O00182-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9	ENST00000395473.7	TSL:1 MANE Select	c.428C>T	p.Ser143Phe	missense	Exon 4 of 11	ENSP00000378856.2	O00182-1
	LGALS9	ENST00000302228.9	TSL:1	c.428C>T	p.Ser143Phe	missense	Exon 4 of 10	ENSP00000306228.5	O00182-2
	LGALS9	ENST00000870767.1		c.428C>T	p.Ser143Phe	missense	Exon 4 of 11	ENSP00000540826.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		-1.0
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.074
Sift	Benign	0.11	T
Sift4G	Benign	0.077	T
Polyphen		0.29	B
Vest4		0.20
MutPred		0.55		Loss of sheet (P = 0.0315)
MVP		0.20
MPC		1.5
ClinPred		0.35	T
GERP RS		0.29
Varity_R		0.29
gMVP		0.26
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

hg19: chr17-25969358;