Variant 1-236544767-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_201544.4(LGALS8):c.656T>C(p.Leu219Pro) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LGALS8
NM_201544.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

Variant links:

Genes affected

LGALS8 (HGNC:6569): (galectin 8) This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

LGALS8 links:

LGALS8 (HGNC:):

LGALS8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27877328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LGALS8	NM_201544.4 linkuse as main transcript	c.656T>C	p.Leu219Pro	missense_variant	9/10	ENST00000366584.9	NP_963838.1	O00214-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LGALS8	ENST00000366584.9 linkuse as main transcript	c.656T>C	p.Leu219Pro	missense_variant	9/10	1	NM_201544.4	ENSP00000355543.4		O00214-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452802

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721948

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.782T>C (p.L261P) alteration is located in exon 11 (coding exon 9) of the LGALS8 gene. This alteration results from a T to C substitution at nucleotide position 782, causing the leucine (L) at amino acid position 261 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.18

.;.;.;T;T;.;T;.;T;T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.81

.;.;.;.;T;T;.;T;T;T;.

M_CAP

Benign

0.012

MetaRNN

Benign

0.28

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

.;.;.;M;.;.;M;.;.;M;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.94

N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.70

P;P;P;P;P;P;P;.;.;P;P

Vest4

0.47

MutPred

0.70

.;.;.;Loss of stability (P = 0.0145);.;.;Loss of stability (P = 0.0145);.;.;Loss of stability (P = 0.0145);.;

MVP

0.42

MPC

0.20

ClinPred

0.24

GERP RS

0.40

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.42

gMVP

0.82

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over