11-66042593-C-T

Variant names:

• chr11-66042593-C-T
• rs756451940
• NM_033036.3:c.1210G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033036.3(GAL3ST3):​c.1210G>A​(p.Gly404Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,535,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: GAL3ST3 NM_033036.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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]

ACMG classification

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=0.074600905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL3ST3	NM_033036.3	c.1210G>A	p.Gly404Ser	missense_variant	Exon 3 of 3	ENST00000312006.5	NP_149025.1
GAL3ST3	XM_017018519.2	c.1276G>A	p.Gly426Ser	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	c.1210G>A	p.Gly404Ser	missense_variant	Exon 3 of 3	1	NM_033036.3	ENSP00000308591.3
GAL3ST3	ENST00000527878.1	c.1210G>A	p.Gly404Ser	missense_variant	Exon 2 of 2	1		ENSP00000434829.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 151914 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000221

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000150 AC: 20 AN: 133100 Hom.: 0 AF XY: 0.000137 AC XY: 10 AN XY: 72962

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000208

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000231 AC: 320 AN: 1383920 Hom.: 0 Cov.: 33 AF XY: 0.000231 AC XY: 158 AN XY: 683064

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.000197

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000253

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000272

Gnomad4 OTH exome AF: 0.000294

GnomAD4 genome AF: 0.000125 AC: 19 AN: 151914 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74184

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000285 Hom.: 0

Bravo AF: 0.000162

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000826 AC: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 27, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1210G>A (p.G404S) 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 1210, causing the glycine (G) at amino acid position 404 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	-0.46	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.0013	T;T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.51	.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.33	N;N
REVEL	Benign	0.059
Sift	Benign	0.14	T;T
Sift4G	Benign	0.50	T;T
Polyphen		0.99	D;D
Vest4		0.11
MutPred		0.28		Gain of phosphorylation at G404 (P = 0.0014);Gain of phosphorylation at G404 (P = 0.0014);
MVP		0.29
MPC		0.73
ClinPred		0.037	T
GERP RS		3.3
Varity_R		0.060
gMVP		0.41

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

Other links and lift over

dbSNP: rs756451940; hg19: chr11-65810064;