11-66042738-C-T

Variant names:

• chr11-66042738-C-T
• rs61895584
• NM_033036.3:c.1065G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_033036.3(GAL3ST3):​c.1065G>A​(p.Pro355Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 1,532,628 control chromosomes in the GnomAD database, including 562,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (47277 hom., cov: 32)
  • Exomes 𝑓: 0.86 (514959 hom.)
• Consequence: GAL3ST3 NM_033036.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.20
• Publications: 11 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 11-66042738-C-T is Benign according to our data. Variant chr11-66042738-C-T is described in ClinVar as Benign. ClinVar VariationId is 1293586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.2 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.862 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.1065G>A	p.Pro355Pro	synonymous	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.1065G>A	p.Pro355Pro	synonymous	Exon 3 of 3	ENSP00000308591.3	Q96A11
	GAL3ST3	ENST00000527878.1	TSL:1	c.1065G>A	p.Pro355Pro	synonymous	Exon 2 of 2	ENSP00000434829.1	Q96A11
	GAL3ST3	ENST00000882250.1		c.1065G>A	p.Pro355Pro	synonymous	Exon 3 of 3	ENSP00000552309.1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 117945 AN: 151482 Hom.: 47253 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.835

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.796

Gnomad NFE AF: 0.868

Gnomad OTH AF: 0.788

GnomAD2 exomes AF: 0.845 AC: 107684 AN: 127488 AF XY: 0.846

Gnomad AFR exome AF: 0.571

Gnomad AMR exome AF: 0.893

Gnomad ASJ exome AF: 0.858

Gnomad EAS exome AF: 0.770

Gnomad FIN exome AF: 0.841

Gnomad NFE exome AF: 0.869

Gnomad OTH exome AF: 0.855

GnomAD4 exome AF: 0.862 AC: 1190343 AN: 1381040 Hom.: 514959 Cov.: 62 AF XY: 0.862 AC XY: 587346 AN XY: 681442

African (AFR) AF: 0.566 AC: 17760 AN: 31358

American (AMR) AF: 0.887 AC: 31527 AN: 35532

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 21528 AN: 25060

East Asian (EAS) AF: 0.799 AC: 28446 AN: 35618

South Asian (SAS) AF: 0.846 AC: 66873 AN: 79086

European-Finnish (FIN) AF: 0.851 AC: 28506 AN: 33488

Middle Eastern (MID) AF: 0.801 AC: 4455 AN: 5564

European-Non Finnish (NFE) AF: 0.875 AC: 942527 AN: 1077590

Other (OTH) AF: 0.844 AC: 48721 AN: 57744

GnomAD4 genome AF: 0.778 AC: 118011 AN: 151588 Hom.: 47277 Cov.: 32 AF XY: 0.781 AC XY: 57843 AN XY: 74090

African (AFR) AF: 0.575 AC: 23816 AN: 41392

American (AMR) AF: 0.840 AC: 12819 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2957 AN: 3462

East Asian (EAS) AF: 0.776 AC: 3956 AN: 5100

South Asian (SAS) AF: 0.835 AC: 4035 AN: 4830

European-Finnish (FIN) AF: 0.852 AC: 8929 AN: 10484

Middle Eastern (MID) AF: 0.805 AC: 235 AN: 292

European-Non Finnish (NFE) AF: 0.868 AC: 58782 AN: 67752

Other (OTH) AF: 0.785 AC: 1654 AN: 2108

Alfa AF: 0.822 Hom.: 11083

Bravo AF: 0.770

Asia WGS AF: 0.772 AC: 2676 AN: 3468

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
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.8
DANN	Benign	0.82
PhyloP100		-4.2
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: rs61895584; hg19: chr11-65810209; COSMIC: COSV61748592; COSMIC: COSV61748592;