11-66042641-C-T

Variant names:

• chr11-66042641-C-T
• rs1158789711
• NM_033036.3:c.1162G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_033036.3(GAL3ST3):​c.1162G>A​(p.Glu388Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 1,535,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GAL3ST3 NM_033036.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.58
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.971

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.1162G>A	p.Glu388Lys	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.1162G>A	p.Glu388Lys	missense	Exon 3 of 3	ENSP00000308591.3	Q96A11
	GAL3ST3	ENST00000527878.1	TSL:1	c.1162G>A	p.Glu388Lys	missense	Exon 2 of 2	ENSP00000434829.1	Q96A11
	GAL3ST3	ENST00000882250.1		c.1162G>A	p.Glu388Lys	missense	Exon 3 of 3	ENSP00000552309.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151832 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383852 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 683020

African (AFR) AF: 0.00 AC: 0 AN: 31694

American (AMR) AF: 0.00 AC: 0 AN: 35668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 36088

South Asian (SAS) AF: 0.00 AC: 0 AN: 79248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33708

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078784

Other (OTH) AF: 0.00 AC: 0 AN: 57870

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151832 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74146

African (AFR) AF: 0.00 AC: 0 AN: 41398

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67910

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.6
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.035	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.93		Gain of MoRF binding (P = 0.012)
MVP		0.72
MPC		1.1
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.63
gMVP		0.99
Mutation Taster		=40/60	disease causing

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: rs1158789711; hg19: chr11-65810112;