chr17-18488984-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040078.3(LGALS9C):​c.488C>G​(p.Pro163Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. P163L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000022 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS9C NM_001040078.3 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10203856).

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>G	p.Pro163Arg	missense	Exon 5 of 11	NP_001035167.2	Q6DKI2
	LGALS9C	NM_001438918.1		c.488C>G	p.Pro163Arg	missense	Exon 5 of 11	NP_001425847.1
	LGALS9C	NM_001438921.1		c.488C>G	p.Pro163Arg	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>G	p.Pro163Arg	missense	Exon 5 of 11	ENSP00000329932.6	Q6DKI2
	LGALS9C	ENST00000892832.1		c.488C>G	p.Pro163Arg	missense	Exon 5 of 11	ENSP00000562891.1
	LGALS9C	ENST00000583322.5	TSL:5	c.444+1227C>G		intron	N/A	ENSP00000462708.1	J3KSY2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 236930 AF XY: 0.0000234

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000191

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000220 AC: 3 AN: 1365218 Hom.: 1 Cov.: 32 AF XY: 0.00000442 AC XY: 3 AN XY: 679344

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

African (AFR) AF: 0.00 AC: 0 AN: 32822

American (AMR) AF: 0.00 AC: 0 AN: 43494

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39624

South Asian (SAS) AF: 0.00 AC: 0 AN: 82056

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3950

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1032820

Other (OTH) AF: 0.00 AC: 0 AN: 56754

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000344 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.9
DANN	Benign	0.85
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.013	N
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.41
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.063
Sift	Benign	0.24	T
Sift4G	Uncertain	0.032	D
Polyphen		0.64	P
Vest4		0.26
MutPred		0.27		Gain of MoRF binding (P = 0.0211)
MVP		0.068
ClinPred		0.075	T
GERP RS		0.38
Varity_R		0.034
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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;