17-18485954-C-T

Variant names:

• chr17-18485954-C-T
• rs754982258
• NM_001040078.3:c.152C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001040078.3(LGALS9C):​c.152C>T​(p.Thr51Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000037 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000059 (17 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS9C NM_001040078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.277
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19476351).

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.152C>T	p.Thr51Met	missense	Exon 3 of 11	NP_001035167.2	Q6DKI2
	LGALS9C	NM_001438918.1		c.152C>T	p.Thr51Met	missense	Exon 3 of 11	NP_001425847.1
	LGALS9C	NM_001438919.1		c.152C>T	p.Thr51Met	missense	Exon 3 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.152C>T	p.Thr51Met	missense	Exon 3 of 11	ENSP00000329932.6	Q6DKI2
	LGALS9C	ENST00000892832.1		c.152C>T	p.Thr51Met	missense	Exon 3 of 11	ENSP00000562891.1
	LGALS9C	ENST00000583322.5	TSL:5	c.152C>T	p.Thr51Met	missense	Exon 3 of 10	ENSP00000462708.1	J3KSY2

Frequencies

GnomAD3 genomes AF: 0.0000371 AC: 4 AN: 107916 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.000119

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000293 AC: 5 AN: 170770 AF XY: 0.0000219

Gnomad AFR exome AF: 0.0000799

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000592 AC: 68 AN: 1147700 Hom.: 17 Cov.: 26 AF XY: 0.0000454 AC XY: 26 AN XY: 572354

African (AFR) AF: 0.000228 AC: 7 AN: 30724

American (AMR) AF: 0.00 AC: 0 AN: 40170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19822

East Asian (EAS) AF: 0.000202 AC: 8 AN: 39518

South Asian (SAS) AF: 0.0000667 AC: 5 AN: 75000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4406

European-Non Finnish (NFE) AF: 0.0000543 AC: 46 AN: 847138

Other (OTH) AF: 0.0000413 AC: 2 AN: 48484

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000371 AC: 4 AN: 107916 Hom.: 0 Cov.: 16 AF XY: 0.0000573 AC XY: 3 AN XY: 52316

African (AFR) AF: 0.000119 AC: 4 AN: 33744

American (AMR) AF: 0.00 AC: 0 AN: 10864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4720

South Asian (SAS) AF: 0.00 AC: 0 AN: 3286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 44296

Other (OTH) AF: 0.00 AC: 0 AN: 1380

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000687 AC: 7

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	0.10
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.54
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.036	N
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.28
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.098
Sift	Benign	0.070	T
Sift4G	Benign	0.12	T
Polyphen		0.85	P
Vest4		0.32
MVP		0.043
ClinPred		0.15	T
GERP RS		-6.7
Varity_R		0.043
gMVP		0.36
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs754982258; hg19: chr17-18389268; COSMIC: COSV105898366; COSMIC: COSV105898366;