17-20453041-C-G

Position:

• chr17-20453041-C-G

Variant summary

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

The NM_001367292.2(LGALS9B):​c.603G>C​(p.Gln201His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,265,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.0000016 (1 hom.)
• Consequence: LGALS9B NM_001367292.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.64

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=0.05527562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS9B	NM_001367292.2	c.603G>C	p.Gln201His	missense_variant	7/11	ENST00000423676.8	NP_001354221.1
LGALS9B	NM_001042685.3	c.603G>C	p.Gln201His	missense_variant	7/11		NP_001036150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS9B	ENST00000423676.8	c.603G>C	p.Gln201His	missense_variant	7/11	1	NM_001367292.2	ENSP00000388841.3

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1265626 Hom.: 1 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 630962

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: 0.00000212

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 18

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 05, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.083
DANN	Benign	0.14
DEOGEN2	Benign	0.0045	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00096	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.024
Sift	Benign	0.58	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.0010	B;B
Vest4		0.14
MutPred		0.20		Gain of glycosylation at T199 (P = 0.0589);Gain of glycosylation at T199 (P = 0.0589);
MVP		0.014
ClinPred		0.079	T
GERP RS		-4.2
Varity_R		0.044
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2042661687; hg19: chr17-20356354;