NM_033036.3:c.1229A>G

Variant names:

• chr11-66042574-T-C
• rs4565902
• NM_033036.3:c.1229A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033036.3(GAL3ST3):​c.1229A>G​(p.Glu410Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E410A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GAL3ST3 NM_033036.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.929
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0691832).

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.1229A>G	p.Glu410Gly	missense	Exon 3 of 3	NP_149025.1	Q96A11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST3	ENST00000312006.5	TSL:1 MANE Select	c.1229A>G	p.Glu410Gly	missense	Exon 3 of 3	ENSP00000308591.3	Q96A11
	GAL3ST3	ENST00000527878.1	TSL:1	c.1229A>G	p.Glu410Gly	missense	Exon 2 of 2	ENSP00000434829.1	Q96A11
	GAL3ST3	ENST00000882250.1		c.1229A>G	p.Glu410Gly	missense	Exon 3 of 3	ENSP00000552309.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1381010 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 681742

African (AFR) AF: 0.00 AC: 0 AN: 31322

American (AMR) AF: 0.00 AC: 0 AN: 34818

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24838

East Asian (EAS) AF: 0.00 AC: 0 AN: 36304

South Asian (SAS) AF: 0.00 AC: 0 AN: 78696

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078498

Other (OTH) AF: 0.00 AC: 0 AN: 57694

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.93
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.039
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.33	T
Polyphen		0.049	B
Vest4		0.14
MutPred		0.17		Gain of MoRF binding (P = 0.0381)
MVP		0.38
MPC		0.86
ClinPred		0.14	T
GERP RS		2.8
Varity_R		0.16
gMVP		0.34
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs4565902; hg19: chr11-65810045;