2-241803442-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_022134.3(GAL3ST2):​c.473C>T​(p.Ala158Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GAL3ST2
NM_022134.3 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.05
Variant links:
Genes affected
GAL3ST2 (HGNC:24869): (galactose-3-O-sulfotransferase 2) 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 hydroxyl at C-3 of nonreducing beta-galactosyl residues, and it can act on both type 1 and type 2 (Galbeta 1-3/1-4GlcNAc-R) oligosaccharides with similar efficiencies, and on core 1 glycans. This enzyme has been implicated in tumor metastasis processes. This gene is different from the GAL3ST3 gene located on chromosome 11, which has also been referred to as GAL3ST2 and encodes a related enzyme with distinct tissue distribution and substrate specificities, compared to galactose-3-O-sulfotransferase 2. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.047786206).
BP6
Variant 2-241803442-C-T is Benign according to our data. Variant chr2-241803442-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2310969.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GAL3ST2NM_022134.3 linkc.473C>T p.Ala158Val missense_variant Exon 4 of 4 ENST00000192314.7 NP_071417.2 Q9H3Q3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GAL3ST2ENST00000192314.7 linkc.473C>T p.Ala158Val missense_variant Exon 4 of 4 1 NM_022134.3 ENSP00000192314.6 Q9H3Q3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459714
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726022
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000449
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000756
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 07, 2022
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.094
BayesDel_addAF
Benign
-0.40
T
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.086
DANN
Benign
0.93
DEOGEN2
Benign
0.0023
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.00057
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
-0.23
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.59
N
REVEL
Benign
0.0060
Sift
Benign
0.34
T
Sift4G
Benign
0.81
T
Polyphen
0.0040
B
Vest4
0.081
MutPred
0.38
Loss of catalytic residue at A158 (P = 0.0845);
MVP
0.030
MPC
0.44
ClinPred
0.11
T
GERP RS
-2.5
Varity_R
0.038
gMVP
0.30

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: rs939445638; hg19: chr2-242742857; API