17-20451537-A-T

Position:

• chr17-20451537-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367292.2(LGALS9B):​c.868T>A​(p.Ser290Thr) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 14)
• Consequence: LGALS9B NM_001367292.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.39

Genes affected

LGALS9B (HGNC:24842): (galectin 9B) This gene was initially thought to represent a pseudogene of galectin 9; however, this transcript has good exon-intron structure and encodes a predicted protein of the same size as and highly similar to galectin 9. This gene is one of two similar loci on chromosome 17p similar to galectin 9 and now thought to be protein-encoding. This gene is the more centromeric 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=0.08392057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2	c.868T>A	p.Ser290Thr	missense_variant	10/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3	c.865T>A	p.Ser289Thr	missense_variant	10/11		NP_001036150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9B	ENST00000423676.8	c.868T>A	p.Ser290Thr	missense_variant	10/11	1	NM_001367292.2	ENSP00000388841	P4
LGALS9B	ENST00000324290.5	c.865T>A	p.Ser289Thr	missense_variant	10/11	5		ENSP00000315564	A1
LGALS9B	ENST00000578481.5	c.*668T>A		3_prime_UTR_variant, NMD_transcript_variant	9/10	2		ENSP00000464627

Frequencies

GnomAD3 genomes Cov.: 14

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 14

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.865T>A (p.S289T) alteration is located in exon 10 (coding exon 10) of the LGALS9B gene. This alteration results from a T to A substitution at nucleotide position 865, causing the serine (S) at amino acid position 289 to be replaced by a threonine (T). 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	Benign	0.090
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.2
DANN	Benign	0.88
DEOGEN2	Benign	0.0042	T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.10	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.41	T
REVEL	Benign	0.012
Sift4G	Benign	0.38	T;T
Polyphen		0.32	B;B
Vest4		0.21
MutPred		0.37		Loss of disorder (P = 0.09);.;
MVP		0.014
ClinPred		0.12	T
GERP RS		-0.37
Varity_R		0.075
gMVP		0.17

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: chr17-20354850;