rs1126407

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_201544.4(LGALS8):​c.56T>A​(p.Phe19Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 1,564,154 control chromosomes in the GnomAD database, including 347,465 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.61 ( 29286 hom., cov: 32)
Exomes 𝑓: 0.66 ( 318179 hom. )

Consequence

LGALS8
NM_201544.4 missense

Scores

1
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=4.5207125E-6).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LGALS8NM_201544.4 linkuse as main transcriptc.56T>A p.Phe19Tyr missense_variant 3/10 ENST00000366584.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LGALS8ENST00000366584.9 linkuse as main transcriptc.56T>A p.Phe19Tyr missense_variant 3/101 NM_201544.4 P1O00214-1

Frequencies

GnomAD3 genomes
AF:
0.611
AC:
92806
AN:
151824
Hom.:
29267
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.494
Gnomad AMI
AF:
0.593
Gnomad AMR
AF:
0.574
Gnomad ASJ
AF:
0.609
Gnomad EAS
AF:
0.484
Gnomad SAS
AF:
0.458
Gnomad FIN
AF:
0.751
Gnomad MID
AF:
0.525
Gnomad NFE
AF:
0.690
Gnomad OTH
AF:
0.607
GnomAD3 exomes
AF:
0.611
AC:
152862
AN:
250140
Hom.:
48131
AF XY:
0.610
AC XY:
82517
AN XY:
135244
show subpopulations
Gnomad AFR exome
AF:
0.489
Gnomad AMR exome
AF:
0.532
Gnomad ASJ exome
AF:
0.600
Gnomad EAS exome
AF:
0.486
Gnomad SAS exome
AF:
0.472
Gnomad FIN exome
AF:
0.736
Gnomad NFE exome
AF:
0.686
Gnomad OTH exome
AF:
0.629
GnomAD4 exome
AF:
0.664
AC:
937110
AN:
1412210
Hom.:
318179
Cov.:
31
AF XY:
0.658
AC XY:
464228
AN XY:
705084
show subpopulations
Gnomad4 AFR exome
AF:
0.484
Gnomad4 AMR exome
AF:
0.533
Gnomad4 ASJ exome
AF:
0.599
Gnomad4 EAS exome
AF:
0.472
Gnomad4 SAS exome
AF:
0.478
Gnomad4 FIN exome
AF:
0.739
Gnomad4 NFE exome
AF:
0.696
Gnomad4 OTH exome
AF:
0.637
GnomAD4 genome
AF:
0.611
AC:
92872
AN:
151944
Hom.:
29286
Cov.:
32
AF XY:
0.608
AC XY:
45190
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.494
Gnomad4 AMR
AF:
0.574
Gnomad4 ASJ
AF:
0.609
Gnomad4 EAS
AF:
0.485
Gnomad4 SAS
AF:
0.459
Gnomad4 FIN
AF:
0.751
Gnomad4 NFE
AF:
0.690
Gnomad4 OTH
AF:
0.605
Alfa
AF:
0.665
Hom.:
25638
Bravo
AF:
0.591
TwinsUK
AF:
0.701
AC:
2598
ALSPAC
AF:
0.693
AC:
2672
ESP6500AA
AF:
0.493
AC:
2173
ESP6500EA
AF:
0.683
AC:
5870
ExAC
AF:
0.609
AC:
73977
Asia WGS
AF:
0.452
AC:
1576
AN:
3478
EpiCase
AF:
0.673
EpiControl
AF:
0.664

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
14
DANN
Benign
0.77
DEOGEN2
Benign
0.011
.;.;.;T;.;T;.;.;T;T;.;T;.;T;T;T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.22
T;T;.;T;.;T;.;T;.;T;T;.;T;T;T;.
MetaRNN
Benign
0.0000045
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.72
.;.;N;.;N;.;N;.;N;.;N;N;.;.;N;.
MutationTaster
Benign
1.0
P;P;P;P;P;P;P;P;P;P
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-0.29
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.12
Sift
Benign
1.0
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.89
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.0, 0.0010
.;.;B;.;B;.;B;.;B;B;B;B;.;.;B;B
Vest4
0.098, 0.13, 0.10, 0.14, 0.17, 0.10, 0.14, 0.13, 0.14, 0.12
MPC
0.060
ClinPred
0.0080
T
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.21
gMVP
0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1126407; hg19: chr1-236700807; COSMIC: COSV53023494; COSMIC: COSV53023494; API