NM_001040078.3:c.488C>T

Variant names:

• chr17-18488984-C-T
• rs779017810
• NM_001040078.3:c.488C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040078.3(LGALS9C):​c.488C>T​(p.Pro163Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000072 (0 hom., cov: 22)
  • Exomes 𝑓: 0.000050 (7 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS9C NM_001040078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.409
• Publications: 0 publications found

Genes affected

LGALS9C (HGNC:33874): (galectin 9C) 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 telomeric gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03631562).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9C	NM_001040078.3	MANE Select	c.488C>T	p.Pro163Leu	missense	Exon 5 of 11	NP_001035167.2	Q6DKI2
	LGALS9C	NM_001438918.1		c.488C>T	p.Pro163Leu	missense	Exon 5 of 11	NP_001425847.1
	LGALS9C	NM_001438921.1		c.488C>T	p.Pro163Leu	missense	Exon 5 of 11	NP_001425850.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9C	ENST00000328114.11	TSL:1 MANE Select	c.488C>T	p.Pro163Leu	missense	Exon 5 of 11	ENSP00000329932.6	Q6DKI2
	LGALS9C	ENST00000892832.1		c.488C>T	p.Pro163Leu	missense	Exon 5 of 11	ENSP00000562891.1
	LGALS9C	ENST00000583322.5	TSL:5	c.444+1227C>T		intron	N/A	ENSP00000462708.1	J3KSY2

Frequencies

GnomAD3 genomes AF: 0.00000725 AC: 1 AN: 137922 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000144 AC: 34 AN: 236930 AF XY: 0.000109

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000981

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

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: 0.0000498 AC: 68 AN: 1365214 Hom.: 7 Cov.: 32 AF XY: 0.0000397 AC XY: 27 AN XY: 679342

African (AFR) AF: 0.0000305 AC: 1 AN: 32822

American (AMR) AF: 0.000874 AC: 38 AN: 43488

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24304

East Asian (EAS) AF: 0.000379 AC: 15 AN: 39626

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49394

Middle Eastern (MID) AF: 0.000253 AC: 1 AN: 3950

European-Non Finnish (NFE) AF: 0.00000484 AC: 5 AN: 1032820

Other (OTH) AF: 0.000123 AC: 7 AN: 56754

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000724 AC: 1 AN: 138042 Hom.: 0 Cov.: 22 AF XY: 0.0000149 AC XY: 1 AN XY: 67218

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 39306

American (AMR) AF: 0.00 AC: 0 AN: 13992

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3126

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60322

Other (OTH) AF: 0.00 AC: 0 AN: 1888

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000775 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.0
DANN	Benign	0.54
DEOGEN2	Benign	0.030	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.010	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.41
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.024
Sift	Benign	0.15	T
Sift4G	Uncertain	0.048	D
Polyphen		0.016	B
Vest4		0.15
MutPred		0.36		Loss of glycosylation at S160 (P = 0.08)
MVP		0.043
ClinPred		0.012	T
GERP RS		0.38
Varity_R		0.032
gMVP		0.15
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs779017810; hg19: chr17-18392298;