Genetic Variant NM_001040078.3:c.286G>A (chr17-18486088-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001040078.3(LGALS9C):c.286G>A(p.Gly96Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000517 in 1,159,614 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 16)

Exomes 𝑓: 0.0000052 ( 2 hom. )

Consequence

LGALS9C
NM_001040078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.74

Publications

0 publications found

Variant links:

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]

LGALS9C links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGALS9C	NM_001040078.3	MANE Select	c.286G>A	p.Gly96Arg	missense	Exon 3 of 11	NP_001035167.2	Q6DKI2
LGALS9C	NM_001438918.1		c.286G>A	p.Gly96Arg	missense	Exon 3 of 11	NP_001425847.1
LGALS9C	NM_001438919.1		c.286G>A	p.Gly96Arg	missense	Exon 3 of 10	NP_001425848.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LGALS9C	ENST00000328114.11	TSL:1 MANE Select	c.286G>A	p.Gly96Arg	missense	Exon 3 of 11	ENSP00000329932.6	Q6DKI2
LGALS9C	ENST00000892832.1		c.286G>A	p.Gly96Arg	missense	Exon 3 of 11	ENSP00000562891.1
LGALS9C	ENST00000583322.5	TSL:5	c.286G>A	p.Gly96Arg	missense	Exon 3 of 10	ENSP00000462708.1	J3KSY2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000193

AC:

AN:

207476

AF XY:

0.0000179

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000461

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000517

AC:

AN:

1159614

Hom.:

Cov.:

AF XY:

0.00000173

AC XY:

AN XY:

577760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30688

American (AMR)

AF:

0.00

AC:

AN:

40532

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19908

East Asian (EAS)

AF:

0.00

AC:

AN:

39570

South Asian (SAS)

AF:

0.00

AC:

AN:

74826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4600

European-Non Finnish (NFE)

AF:

0.00000699

AC:

AN:

858042

Other (OTH)

AF:

0.00

AC:

AN:

48894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.5

PhyloP100

4.7

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.23

Sift

Uncertain

0.027

Sift4G

Uncertain

0.015

Polyphen

0.99

Vest4

0.75

MutPred

0.75

Gain of solvent accessibility (P = 0.006)

MVP

0.14

ClinPred

0.95

GERP RS

3.0

Varity_R

0.62

gMVP

0.67

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over