Genetic Variant GAL3ST3:p.Arg408Leu (chr11-66042580-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_033036.3(GAL3ST3):c.1223G>T(p.Arg408Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,383,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GAL3ST3
NM_033036.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL3ST3	NM_033036.3 link	c.1223G>T	p.Arg408Leu	missense_variant	Exon 3 of 3	ENST00000312006.5	NP_149025.1	Q96A11
GAL3ST3	XM_017018519.2 link	c.1289G>T	p.Arg430Leu	missense_variant	Exon 2 of 2		XP_016874008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAL3ST3	ENST00000312006.5 link	c.1223G>T	p.Arg408Leu	missense_variant	Exon 3 of 3	1	NM_033036.3	ENSP00000308591.3		Q96A11
GAL3ST3	ENST00000527878.1 link	c.1223G>T	p.Arg408Leu	missense_variant	Exon 2 of 2	1		ENSP00000434829.1		Q96A11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1383196

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

682776

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:

0.00000185

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1223G>T (p.R408L) alteration is located in exon 3 (coding exon 2) of the GAL3ST3 gene. This alteration results from a G to T substitution at nucleotide position 1223, causing the arginine (R) at amino acid position 408 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

0.082

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0030

T;T

Eigen

Benign

0.14

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.58

.;T

M_CAP

Benign

0.0075

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.0

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.010

D;D

Sift4G

Benign

0.23

T;T

Polyphen

1.0

D;D

Vest4

0.52

MutPred

0.32

Loss of methylation at R408 (P = 0.0151);Loss of methylation at R408 (P = 0.0151);

MVP

0.58

MPC

0.90

ClinPred

0.69

GERP RS

4.1

Varity_R

0.16

gMVP

0.47

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over