17-27645868-C-T

Variant names:

• chr17-27645868-C-T
• NM_009587.3:c.584C>T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.128

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

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
LGALS9	NM_009587.3	c.584C>T	p.Thr195Ile	missense_variant	Exon 7 of 11	ENST00000395473.7	NP_033665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS9	ENST00000395473.7	c.584C>T	p.Thr195Ile	missense_variant	Exon 7 of 11	1	NM_009587.3	ENSP00000378856.2

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

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

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;