rs4985834

chr17-20467454-G-Achr17-20467454-G-Cchr17-20467454-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001367292.2(LGALS9B):c.17C>T(p.Ser6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 49,430 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S6C) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 7)
  • Exomes 𝑓: 0.000019 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS9B NM_001367292.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, LGALS9B
• BP4: Computational evidence support a benign effect (MetaRNN=0.078609526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LGALS9B	NM_001367292.2	c.17C>T	p.Ser6Phe	missense_variant	1/11	ENST00000423676.8
LGALS9B	NM_001042685.3	c.17C>T	p.Ser6Phe	missense_variant	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LGALS9B	ENST00000423676.8	c.17C>T	p.Ser6Phe	missense_variant	1/11	1	NM_001367292.2	P4
LGALS9B	ENST00000324290.5	c.17C>T	p.Ser6Phe	missense_variant	1/11	5		A1
LGALS9B	ENST00000578481.5	c.17C>T	p.Ser6Phe	missense_variant, NMD_transcript_variant	1/10	2

Frequencies

GnomAD3 genomes AF: 0.0000405 AC: 2 AN: 49430 Hom.: 0 Cov.: 7

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000192 AC: 8 AN: 417406 Hom.: 2 Cov.: 6 AF XY: 0.0000284 AC XY: 6 AN XY: 211566

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: 0.0000277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000405 AC: 2 AN: 49430 Hom.: 0 Cov.: 7 AF XY: 0.0000437 AC XY: 1 AN XY: 22866

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000736

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	3.0
Dann	Benign	0.79
DEOGEN2	Benign	0.0058	T;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.018
Sift	Benign	0.13	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.12	B;B
Vest4		0.14
MutPred		0.26		Loss of disorder (P = 0.0053);Loss of disorder (P = 0.0053);
MVP		0.030
ClinPred		0.12	T
GERP RS		-0.15
Varity_R		0.048
gMVP		0.13

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: rs4985834; hg19: chr17-20370767;