NM_009587.3:c.13G>T

Variant names:

• chr17-27631278-G-T
• rs3751093
• NM_009587.3:c.13G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_009587.3(LGALS9):​c.13G>T​(p.Gly5Cys) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LGALS9 NM_009587.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.69
• Publications: 40 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]

ENSG00000266728 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067805916).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9	NM_009587.3	MANE Select	c.13G>T	p.Gly5Cys	missense	Exon 1 of 11	NP_033665.1
	LGALS9	NM_002308.4		c.13G>T	p.Gly5Cys	missense	Exon 1 of 10	NP_002299.2
	LGALS9	NM_001330163.2		c.13G>T	p.Gly5Cys	missense	Exon 1 of 9	NP_001317092.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9	ENST00000395473.7	TSL:1 MANE Select	c.13G>T	p.Gly5Cys	missense	Exon 1 of 11	ENSP00000378856.2
	LGALS9	ENST00000302228.9	TSL:1	c.13G>T	p.Gly5Cys	missense	Exon 1 of 10	ENSP00000306228.5
	ENSG00000266728	ENST00000584605.5	TSL:2	n.*24-6985G>T		intron	N/A	ENSP00000463557.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 7932

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.046
DANN	Benign	0.75
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.95	L
PhyloP100		-3.7
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.011
Sift	Benign	0.20	T
Sift4G	Benign	0.23	T
Polyphen		0.0010	B
Vest4		0.060
MutPred		0.27		Loss of disorder (P = 0.0266)
MVP		0.18
MPC		0.30
ClinPred		0.057	T
GERP RS		-5.4
PromoterAI		-0.035	Neutral
Varity_R		0.24
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

dbSNP: rs3751093; hg19: chr17-25958304;