11-66042574-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033036.3(GAL3ST3):​c.1229A>C​(p.Glu410Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,530,860 control chromosomes in the GnomAD database, including 19,287 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E410K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.17 (2317 hom., cov: 31)
  • Exomes 𝑓: 0.15 (16970 hom.)
• Consequence: GAL3ST3 NM_033036.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.929
• Publications: 14 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.001140058).
• BP6: Variant 11-66042574-T-G is Benign according to our data. Variant chr11-66042574-T-G is described in ClinVar as Benign. ClinVar VariationId is 1179723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

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>C	p.Glu410Ala	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>C	p.Glu410Ala	missense	Exon 3 of 3	ENSP00000308591.3	Q96A11
	GAL3ST3	ENST00000527878.1	TSL:1	c.1229A>C	p.Glu410Ala	missense	Exon 2 of 2	ENSP00000434829.1	Q96A11
	GAL3ST3	ENST00000882250.1		c.1229A>C	p.Glu410Ala	missense	Exon 3 of 3	ENSP00000552309.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26024 AN: 151454 Hom.: 2316 Cov.: 31

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0985

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.188

GnomAD2 exomes AF: 0.142 AC: 18585 AN: 130828 AF XY: 0.147

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.0926

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.107

Gnomad FIN exome AF: 0.159

Gnomad NFE exome AF: 0.150

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.153 AC: 211473 AN: 1379292 Hom.: 16970 Cov.: 32 AF XY: 0.154 AC XY: 105106 AN XY: 680876

African (AFR) AF: 0.216 AC: 6733 AN: 31180

American (AMR) AF: 0.100 AC: 3468 AN: 34626

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 4133 AN: 24764

East Asian (EAS) AF: 0.102 AC: 3697 AN: 36268

South Asian (SAS) AF: 0.168 AC: 13185 AN: 78528

European-Finnish (FIN) AF: 0.154 AC: 5163 AN: 33468

Middle Eastern (MID) AF: 0.219 AC: 1168 AN: 5334

European-Non Finnish (NFE) AF: 0.153 AC: 164823 AN: 1077562

Other (OTH) AF: 0.158 AC: 9103 AN: 57562

GnomAD4 genome AF: 0.172 AC: 26036 AN: 151568 Hom.: 2317 Cov.: 31 AF XY: 0.172 AC XY: 12712 AN XY: 74082

African (AFR) AF: 0.212 AC: 8774 AN: 41368

American (AMR) AF: 0.149 AC: 2276 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3462

East Asian (EAS) AF: 0.111 AC: 562 AN: 5068

South Asian (SAS) AF: 0.174 AC: 833 AN: 4792

European-Finnish (FIN) AF: 0.153 AC: 1608 AN: 10522

Middle Eastern (MID) AF: 0.259 AC: 75 AN: 290

European-Non Finnish (NFE) AF: 0.159 AC: 10796 AN: 67792

Other (OTH) AF: 0.191 AC: 402 AN: 2104

Alfa AF: 0.177 Hom.: 498

Bravo AF: 0.171

TwinsUK AF: 0.160 AC: 594

ALSPAC AF: 0.146 AC: 561

ESP6500AA AF: 0.0985 AC: 375

ESP6500EA AF: 0.0942 AC: 720

ExAC AF: 0.0628 AC: 6014

Asia WGS AF: 0.172 AC: 600 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.0048	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.0011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.93
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.054
Sift	Uncertain	0.021	D
Sift4G	Benign	0.43	T
Polyphen		0.0	B
Vest4		0.037
MPC		0.78
ClinPred		0.00067	T
GERP RS		2.8
Varity_R		0.12
gMVP		0.32
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV61748778; COSMIC: COSV61748778;