11-66042604-T-G

Variant names:

• chr11-66042604-T-G
• NM_033036.3:c.1199A>C

Variant summary

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

The NM_033036.3(GAL3ST3):​c.1199A>C​(p.Lys400Thr) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GAL3ST3 NM_033036.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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=0.16738904).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL3ST3	NM_033036.3	c.1199A>C	p.Lys400Thr	missense_variant	Exon 3 of 3	ENST00000312006.5	NP_149025.1
GAL3ST3	XM_017018519.2	c.1265A>C	p.Lys422Thr	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.1199A>C	p.Lys400Thr	missense_variant	Exon 3 of 3	1	NM_033036.3	ENSP00000308591.3
GAL3ST3	ENST00000527878.1	c.1199A>C	p.Lys400Thr	missense_variant	Exon 2 of 2	1		ENSP00000434829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1384970 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 683710

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 24, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1199A>C (p.K400T) alteration is located in exon 3 (coding exon 2) of the GAL3ST3 gene. This alteration results from a A to C substitution at nucleotide position 1199, causing the lysine (K) at amino acid position 400 to be replaced by a threonine (T). 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	0.28
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0065	T;T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.61	.;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.93	N;N
REVEL	Benign	0.032
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.31	T;T
Polyphen		0.28	B;B
Vest4		0.34
MutPred		0.42		Loss of methylation at K400 (P = 0.0012);Loss of methylation at K400 (P = 0.0012);
MVP		0.44
MPC		0.89
ClinPred		0.18	T
GERP RS		3.6
Varity_R		0.14
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-65810075;