NM_001040078.3:c.167A>T

Variant names:

• chr17-18485969-A-T
• rs748067837
• NM_001040078.3:c.167A>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.167A>T​(p.Asn56Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., cov: 16)
  • Exomes 𝑓: 0.0000035 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LGALS9C NM_001040078.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.156
• 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=0.25328726).

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.167A>T	p.Asn56Ile	missense	Exon 3 of 11	NP_001035167.2	Q6DKI2
	LGALS9C	NM_001438918.1		c.167A>T	p.Asn56Ile	missense	Exon 3 of 11	NP_001425847.1
	LGALS9C	NM_001438919.1		c.167A>T	p.Asn56Ile	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.167A>T	p.Asn56Ile	missense	Exon 3 of 11	ENSP00000329932.6	Q6DKI2
	LGALS9C	ENST00000892832.1		c.167A>T	p.Asn56Ile	missense	Exon 3 of 11	ENSP00000562891.1
	LGALS9C	ENST00000583322.5	TSL:5	c.167A>T	p.Asn56Ile	missense	Exon 3 of 10	ENSP00000462708.1	J3KSY2

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111530 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.0000584

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: 0.0000114 AC: 2 AN: 174838 AF XY: 0.00

Gnomad AFR exome AF: 0.000156

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000347 AC: 4 AN: 1152878 Hom.: 0 Cov.: 27 AF XY: 0.00000348 AC XY: 2 AN XY: 574672

African (AFR) AF: 0.000130 AC: 4 AN: 30778

American (AMR) AF: 0.00 AC: 0 AN: 40216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19810

East Asian (EAS) AF: 0.00 AC: 0 AN: 39542

South Asian (SAS) AF: 0.00 AC: 0 AN: 74892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4548

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 851896

Other (OTH) AF: 0.00 AC: 0 AN: 48664

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000179 AC: 2 AN: 111530 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 54218

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

African (AFR) AF: 0.0000584 AC: 2 AN: 34228

American (AMR) AF: 0.00 AC: 0 AN: 11286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2470

East Asian (EAS) AF: 0.00 AC: 0 AN: 4842

South Asian (SAS) AF: 0.00 AC: 0 AN: 3396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6780

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 228

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 46138

Other (OTH) AF: 0.00 AC: 0 AN: 1432

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000196 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	Benign	0.24
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Benign	0.39
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.062	N
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.16
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.046
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.019	D
Polyphen		0.85	P
Vest4		0.49
MutPred		0.63		Loss of solvent accessibility (P = 0.0576)
MVP		0.18
ClinPred		0.55	D
GERP RS		-0.43
Varity_R		0.73
gMVP		0.40

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: rs748067837; hg19: chr17-18389283;