rs3751093

Positions:

• chr17-27631278-G-A
• chr17-27631278-G-C
• chr17-27631278-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_009587.3(LGALS9):​c.13G>A​(p.Gly5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,782 control chromosomes in the GnomAD database, including 38,482 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.19 (3029 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35453 hom.)
• Consequence: LGALS9 NM_009587.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.69

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045009255).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS9	NM_009587.3	c.13G>A	p.Gly5Ser	missense_variant	1/11	ENST00000395473.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS9	ENST00000395473.7	c.13G>A	p.Gly5Ser	missense_variant	1/11	1	NM_009587.3	P4

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29465 AN: 152052 Hom.: 3028 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0606

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.225 AC: 56663 AN: 251364 Hom.: 6800 AF XY: 0.226 AC XY: 30669 AN XY: 135860

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.304

Gnomad ASJ exome AF: 0.240

Gnomad EAS exome AF: 0.253

Gnomad SAS exome AF: 0.251

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.218 AC: 318600 AN: 1461610 Hom.: 35453 Cov.: 33 AF XY: 0.219 AC XY: 158968 AN XY: 727124

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.279

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.214

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.194 AC: 29467 AN: 152172 Hom.: 3029 Cov.: 32 AF XY: 0.193 AC XY: 14355 AN XY: 74402

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.214

Alfa AF: 0.197 Hom.: 2514

Bravo AF: 0.197

TwinsUK AF: 0.215 AC: 796

ALSPAC AF: 0.216 AC: 831

ESP6500AA AF: 0.129 AC: 568

ESP6500EA AF: 0.210 AC: 1808

ExAC AF: 0.220 AC: 26736

Asia WGS AF: 0.230 AC: 799 AN: 3478

EpiCase AF: 0.213

EpiControl AF: 0.211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0090
DANN	Benign	0.72
DEOGEN2	Benign	0.086	T;.;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.39	T;T;T;T
MetaRNN	Benign	0.0045	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.17	N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.62	N;N;N;.
REVEL	Benign	0.020
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.0	B;.;.;.
Vest4		0.042
MPC		0.28
ClinPred		0.0038	T
GERP RS		-5.4
Varity_R		0.24
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs3751093; hg19: chr17-25958304; COSMIC: COSV56349194; COSMIC: COSV56349194;