17-20453027-T-A

Position:

• chr17-20453027-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001367292.2(LGALS9B):​c.617A>T​(p.Gln206Leu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 18)
• Consequence: LGALS9B NM_001367292.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.46

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]

LGALS9B (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04792416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2	c.617A>T	p.Gln206Leu	missense_variant	7/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3	c.617A>T	p.Gln206Leu	missense_variant	7/11		NP_001036150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9B	ENST00000423676.8	c.617A>T	p.Gln206Leu	missense_variant	7/11	1	NM_001367292.2	ENSP00000388841.3

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 18

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 22, 2024

The c.617A>T (p.Q206L) alteration is located in exon 7 (coding exon 7) of the LGALS9B gene. This alteration results from a A to T substitution at nucleotide position 617, causing the glutamine (Q) at amino acid position 206 to be replaced by a leucine (L). 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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	6.2
DANN	Benign	0.68
DEOGEN2	Benign	0.043	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.015
Sift	Benign	0.72	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0020	B;B
Vest4		0.24
MutPred		0.32		Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);
MVP		0.030
ClinPred		0.051	T
GERP RS		-2.0
Varity_R		0.19
gMVP		0.18

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-20356340;