Genetic Variant GAL3ST3:p.Arg402Gln (chr11-66042598-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033036.3(GAL3ST3):c.1205G>A(p.Arg402Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,536,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R402W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 1 hom. )

Consequence

GAL3ST3
NM_033036.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.634

Publications

0 publications found

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]

GAL3ST3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01712495).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033036.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST3	NM_033036.3	MANE Select	c.1205G>A	p.Arg402Gln	missense	Exon 3 of 3	NP_149025.1	Q96A11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GAL3ST3	ENST00000312006.5	TSL:1 MANE Select	c.1205G>A	p.Arg402Gln	missense	Exon 3 of 3	ENSP00000308591.3	Q96A11
GAL3ST3	ENST00000527878.1	TSL:1	c.1205G>A	p.Arg402Gln	missense	Exon 2 of 2	ENSP00000434829.1	Q96A11
GAL3ST3	ENST00000882250.1		c.1205G>A	p.Arg402Gln	missense	Exon 3 of 3	ENSP00000552309.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

151896

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000120

AC:

AN:

133706

AF XY:

0.000150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00161

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000387

Gnomad OTH exome

AF:

0.000248

GnomAD4 exome

AF:

0.0000426

AC:

AN:

1384750

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

683528

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31776

American (AMR)

AF:

0.00

AC:

AN:

35684

Ashkenazi Jewish (ASJ)

AF:

0.00155

AC:

AN:

25084

East Asian (EAS)

AF:

0.00

AC:

AN:

36370

South Asian (SAS)

AF:

0.0000505

AC:

AN:

79162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5608

European-Non Finnish (NFE)

AF:

0.00000834

AC:

AN:

1079534

Other (OTH)

AF:

0.000121

AC:

AN:

57916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000329

AC:

AN:

151896

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67946

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000719

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0037

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.076

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.71

M_CAP

Benign

0.0089

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.63

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.59

REVEL

Benign

0.10

Sift

Uncertain

0.013

Sift4G

Benign

0.20

Polyphen

0.97

Vest4

0.11

MVP

0.44

MPC

1.9

ClinPred

0.14

GERP RS

4.2

Varity_R

0.11

gMVP

0.55

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over