Genetic Variant NM_001040078.3:c.740C>T (chr17-18492524-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040078.3(LGALS9C):c.740C>T(p.Thr247Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LGALS9C
NM_001040078.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.875

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1282143).

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.740C>T	p.Thr247Ile	missense	Exon 9 of 11	NP_001035167.2	Q6DKI2
LGALS9C	NM_001438918.1		c.737C>T	p.Thr246Ile	missense	Exon 9 of 11	NP_001425847.1
LGALS9C	NM_001438919.1		c.644C>T	p.Thr215Ile	missense	Exon 8 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.740C>T	p.Thr247Ile	missense	Exon 9 of 11	ENSP00000329932.6	Q6DKI2
LGALS9C	ENST00000577265.5	TSL:1	n.1449C>T		non_coding_transcript_exon	Exon 4 of 6
LGALS9C	ENST00000892832.1		c.737C>T	p.Thr246Ile	missense	Exon 9 of 11	ENSP00000562891.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1419536

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706512

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

44054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25216

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

84392

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5616

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076778

Other (OTH)

AF:

0.00

AC:

AN:

58776

GnomAD4 genome

Cov.:

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

Benign

0.10

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

1.3

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.13

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0053

M_CAP

Benign

0.0026

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

PhyloP100

-0.88

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.012

Sift

Benign

0.14

Sift4G

Benign

0.36

Polyphen

0.039

Vest4

0.11

MutPred

0.49

Loss of catalytic residue at T247 (P = 0.0058)

MVP

0.068

ClinPred

0.040

GERP RS

-0.80

Varity_R

0.062

gMVP

0.28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over