chr11-66042689-C-T

Variant summary

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

The NM_033036.3(GAL3ST3):​c.1114G>A​(p.Gly372Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,533,916 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: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

GAL3ST3
NM_033036.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.642
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=0.09688777).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAL3ST3NM_033036.3 linkc.1114G>A p.Gly372Ser missense_variant Exon 3 of 3 ENST00000312006.5 NP_149025.1 Q96A11
GAL3ST3XM_017018519.2 linkc.1180G>A p.Gly394Ser 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.1114G>A p.Gly372Ser missense_variant Exon 3 of 3 1 NM_033036.3 ENSP00000308591.3 Q96A11
GAL3ST3ENST00000527878.1 linkc.1114G>A p.Gly372Ser missense_variant Exon 2 of 2 1 ENSP00000434829.1 Q96A11

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151822
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000434
AC:
6
AN:
1382094
Hom.:
0
Cov.:
33
AF XY:
0.00000440
AC XY:
3
AN XY:
681966
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000557
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151822
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74152
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1114G>A (p.G372S) alteration is located in exon 3 (coding exon 2) of the GAL3ST3 gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the glycine (G) at amino acid position 372 to be replaced by a serine (S). 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
0.085
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0042
T;T
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.19
N
LIST_S2
Benign
0.57
.;T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.097
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.65
N;N
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.14
N;N
REVEL
Benign
0.095
Sift
Benign
0.31
T;T
Sift4G
Benign
0.63
T;T
Polyphen
0.021
B;B
Vest4
0.16
MutPred
0.49
Gain of glycosylation at G372 (P = 4e-04);Gain of glycosylation at G372 (P = 4e-04);
MVP
0.40
MPC
0.72
ClinPred
0.22
T
GERP RS
3.6
Varity_R
0.090
gMVP
0.48

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: rs1385084556; hg19: chr11-65810160; API