11-66042550-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033036.3(GAL3ST3):​c.1253C>T​(p.Pro418Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000803 in 1,369,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

GAL3ST3
NM_033036.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.317
Variant links:
Genes affected
GAL3ST3 (HGNC:24144): (galactose-3-O-sulfotransferase 3) This gene encodes a member of the galactose-3-O-sulfotransferase protein family. The product of this gene catalyzes sulfonation by transferring a sulfate group to the 3' position of galactose in N-acetyllactosamine in both type 2 (Gal-beta-1-4GlcNAc-R) oligosaccharides and core-2-branched O-glycans, but not on type 1 or core-1-branched structures. This gene, which has also been referred to as GAL3ST2, is different from the GAL3ST2 gene located on chromosome 2 that encodes a related enzyme with distinct tissue distribution and substrate specificities, compared to galactose-3-O-sulfotransferase 3. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10469043).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAL3ST3NM_033036.3 linkc.1253C>T p.Pro418Leu missense_variant Exon 3 of 3 ENST00000312006.5 NP_149025.1 Q96A11
GAL3ST3XM_017018519.2 linkc.1319C>T p.Pro440Leu missense_variant Exon 2 of 2 XP_016874008.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAL3ST3ENST00000312006.5 linkc.1253C>T p.Pro418Leu missense_variant Exon 3 of 3 1 NM_033036.3 ENSP00000308591.3 Q96A11
GAL3ST3ENST00000527878.1 linkc.1253C>T p.Pro418Leu missense_variant Exon 2 of 2 1 ENSP00000434829.1 Q96A11

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000325
AC:
4
AN:
123228
Hom.:
0
AF XY:
0.0000588
AC XY:
4
AN XY:
68078
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 SAS exome
AF:
0.000198
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000803
AC:
11
AN:
1369838
Hom.:
0
Cov.:
30
AF XY:
0.0000133
AC XY:
9
AN XY:
675836
show subpopulations
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:
0.000143
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000509
Hom.:
0
ExAC
AF:
0.00000958
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1253C>T (p.P418L) alteration is located in exon 3 (coding exon 2) of the GAL3ST3 gene. This alteration results from a C to T substitution at nucleotide position 1253, causing the proline (P) at amino acid position 418 to be replaced by a leucine (L). 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
Benign
0.10
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0050
T;T
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.67
.;T
M_CAP
Benign
0.0064
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.060
Sift
Uncertain
0.015
D;D
Sift4G
Benign
0.080
T;T
Polyphen
0.60
P;P
Vest4
0.23
MutPred
0.18
Loss of relative solvent accessibility (P = 0.008);Loss of relative solvent accessibility (P = 0.008);
MVP
0.50
MPC
1.8
ClinPred
0.16
T
GERP RS
4.1
Varity_R
0.074
gMVP
0.29

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: rs781121710; hg19: chr11-65810021; API