17-18487665-C-T

Variant names:

• chr17-18487665-C-T
• rs1598147978
• NM_001040078.3:c.352C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001040078.3(LGALS9C):​c.352C>T​(p.Leu118Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000072 in 1,389,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: LGALS9C NM_001040078.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.770
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0644699).
• BP6: Variant 17-18487665-C-T is Benign according to our data. Variant chr17-18487665-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2313988.Status of the report is criteria_provided_single_submitter, 1 stars.

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.352C>T	p.Leu118Phe	missense	Exon 4 of 11	NP_001035167.2	Q6DKI2
	LGALS9C	NM_001438918.1		c.352C>T	p.Leu118Phe	missense	Exon 4 of 11	NP_001425847.1
	LGALS9C	NM_001438919.1		c.352C>T	p.Leu118Phe	missense	Exon 4 of 10	NP_001425848.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LGALS9C	ENST00000328114.11	TSL:1 MANE Select	c.352C>T	p.Leu118Phe	missense	Exon 4 of 11	ENSP00000329932.6	Q6DKI2
	LGALS9C	ENST00000892832.1		c.352C>T	p.Leu118Phe	missense	Exon 4 of 11	ENSP00000562891.1
	LGALS9C	ENST00000583322.5	TSL:5	c.352C>T	p.Leu118Phe	missense	Exon 4 of 10	ENSP00000462708.1	J3KSY2

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1389092 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690136

⚠️ 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: 33126

American (AMR) AF: 0.00 AC: 0 AN: 43004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24554

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.00 AC: 0 AN: 83840

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4004

European-Non Finnish (NFE) AF: 9.49e-7 AC: 1 AN: 1053450

Other (OTH) AF: 0.00 AC: 0 AN: 57126

⚠️ 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.: 16

Alfa AF: 0.000229 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.088
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.47
DANN	Benign	0.91
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0036	N
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-0.77
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.92	N
REVEL	Benign	0.012
Sift	Benign	0.69	T
Sift4G	Benign	0.70	T
Polyphen		0.0010	B
Vest4		0.20
MutPred		0.47		Loss of stability (P = 0.182)
MVP		0.068
ClinPred		0.046	T
GERP RS		-4.2
Varity_R		0.038
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1598147978; hg19: chr17-18390979;