17-20451525-T-C

Variant names:

• chr17-20451525-T-C
• rs766903779
• NM_001367292.2:c.880A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001367292.2(LGALS9B):​c.880A>G​(p.Ser294Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 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: 13)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS9B NM_001367292.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0511342).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LGALS9B	NM_001367292.2	c.880A>G	p.Ser294Gly	missense_variant	Exon 10 of 11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3	c.877A>G	p.Ser293Gly	missense_variant	Exon 10 of 11		NP_001036150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LGALS9B	ENST00000423676.8	c.880A>G	p.Ser294Gly	missense_variant	Exon 10 of 11	1	NM_001367292.2	ENSP00000388841.3
LGALS9B	ENST00000324290.5	c.877A>G	p.Ser293Gly	missense_variant	Exon 10 of 11	5		ENSP00000315564.5
LGALS9B	ENST00000578481.5	n.*680A>G		non_coding_transcript_exon_variant	Exon 9 of 10	2		ENSP00000464627.1
LGALS9B	ENST00000578481.5	n.*680A>G		3_prime_UTR_variant	Exon 9 of 10	2		ENSP00000464627.1

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD3 exomes AF: 0.00000418 AC: 1 AN: 239428 Hom.: 0 AF XY: 0.00000766 AC XY: 1 AN XY: 130618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000333

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.86e-7 AC: 1 AN: 1458224 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 725204

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 13

ExAC AF: 0.00000825 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.3
DANN	Benign	0.88
DEOGEN2	Benign	0.0056	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.59	T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.87	L;.
PrimateAI	Benign	0.41	T
REVEL	Benign	0.016
Sift4G	Benign	0.46	T;T
Polyphen		0.0040	B;B
Vest4		0.18
MutPred		0.41		Loss of phosphorylation at S294 (P = 0.0422);.;
MVP		0.014
ClinPred		0.028	T
GERP RS		-0.52
Varity_R		0.13
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs766903779; hg19: chr17-20354838;