17-18487709-C-A

Variant names:

• chr17-18487709-C-A
• rs758797764
• NM_001040078.3:c.396C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001040078.3(LGALS9C):​c.396C>A​(p.Asp132Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,557,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000078 (0 hom., cov: 21)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LGALS9C NM_001040078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.39117005).

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.396C>A	p.Asp132Glu	missense	Exon 4 of 11	NP_001035167.2	Q6DKI2
	LGALS9C	NM_001438918.1		c.396C>A	p.Asp132Glu	missense	Exon 4 of 11	NP_001425847.1
	LGALS9C	NM_001438919.1		c.396C>A	p.Asp132Glu	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.396C>A	p.Asp132Glu	missense	Exon 4 of 11	ENSP00000329932.6	Q6DKI2
	LGALS9C	ENST00000892832.1		c.396C>A	p.Asp132Glu	missense	Exon 4 of 11	ENSP00000562891.1
	LGALS9C	ENST00000583322.5	TSL:5	c.396C>A	p.Asp132Glu	missense	Exon 4 of 10	ENSP00000462708.1	J3KSY2

Frequencies

GnomAD3 genomes AF: 0.0000783 AC: 11 AN: 140546 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.0000246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000709

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: 0.0000173 AC: 4 AN: 230628 AF XY: 0.0000240

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000306

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000299

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000141 AC: 20 AN: 1417316 Hom.: 0 Cov.: 31 AF XY: 0.0000114 AC XY: 8 AN XY: 704664

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

African (AFR) AF: 0.0000300 AC: 1 AN: 33300

American (AMR) AF: 0.000116 AC: 5 AN: 43274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25260

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.00 AC: 0 AN: 84018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4022

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1077442

Other (OTH) AF: 0.0000341 AC: 2 AN: 58592

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000359617), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000782 AC: 11 AN: 140630 Hom.: 0 Cov.: 21 AF XY: 0.0000730 AC XY: 5 AN XY: 68456

African (AFR) AF: 0.0000245 AC: 1 AN: 40768

American (AMR) AF: 0.000708 AC: 10 AN: 14118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3256

East Asian (EAS) AF: 0.00 AC: 0 AN: 4948

South Asian (SAS) AF: 0.00 AC: 0 AN: 4344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9492

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60686

Other (OTH) AF: 0.00 AC: 0 AN: 1932

Alfa AF: 0.0000843 Hom.: 0

ExAC AF: 0.0000167 AC: 2

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Benign	0.57
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		1.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.082
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.94	P
Vest4		0.48
MutPred		0.66		Loss of catalytic residue at N137 (P = 0.1736)
MVP		0.27
ClinPred		0.41	T
GERP RS		1.3
Varity_R		0.76
gMVP		0.20
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs758797764; hg19: chr17-18391023;