chr17-27645868-C-T

Variant names:

• chr17-27645868-C-T
• NM_009587.3:c.584C>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.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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS9 NM_009587.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.128
• 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=0.11327356).

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.584C>T	p.Thr195Ile	missense	Exon 7 of 11	NP_033665.1	O00182-1
	LGALS9	NM_002308.4		c.488C>T	p.Thr163Ile	missense	Exon 6 of 10	NP_002299.2	O00182-2
	LGALS9	NM_001330163.2		c.488C>T	p.Thr163Ile	missense	Exon 6 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.584C>T	p.Thr195Ile	missense	Exon 7 of 11	ENSP00000378856.2	O00182-1
	LGALS9	ENST00000302228.9	TSL:1	c.488C>T	p.Thr163Ile	missense	Exon 6 of 10	ENSP00000306228.5	O00182-2
	LGALS9	ENST00000481514.5	TSL:1	n.1293C>T		non_coding_transcript_exon	Exon 2 of 6

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

African (AFR) AF: 0.00 AC: 0 AN: 33140

American (AMR) AF: 0.00 AC: 0 AN: 43624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.00 AC: 0 AN: 85458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.000349 AC: 2 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105494

Other (OTH) AF: 0.00 AC: 0 AN: 59986

GnomAD4 genome Cov.: 28

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	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
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.064	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		-0.13
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.032
Sift	Benign	0.071	T
Sift4G	Benign	0.10	T
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

Other links and lift over

hg19: chr17-25972894;