11-66042610-T-G

Variant names:

• chr11-66042610-T-G
• NM_033036.3:c.1193A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033036.3(GAL3ST3):​c.1193A>C​(p.Lys398Thr) 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. 12/21 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)
• Consequence: GAL3ST3 NM_033036.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.713

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26530287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAL3ST3	NM_033036.3	c.1193A>C	p.Lys398Thr	missense_variant	Exon 3 of 3	ENST00000312006.5	NP_149025.1
GAL3ST3	XM_017018519.2	c.1259A>C	p.Lys420Thr	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.1193A>C	p.Lys398Thr	missense_variant	Exon 3 of 3	1	NM_033036.3	ENSP00000308591.3
GAL3ST3	ENST00000527878.1	c.1193A>C	p.Lys398Thr	missense_variant	Exon 2 of 2	1		ENSP00000434829.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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.1193A>C (p.K398T) 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 1193, causing the lysine (K) at amino acid position 398 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	Pathogenic	0.59
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T;T
Eigen	Benign	0.088
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.090
Sift	Benign	0.064	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.35	B;B
Vest4		0.16
MutPred		0.55		Loss of methylation at K398 (P = 0.0011);Loss of methylation at K398 (P = 0.0011);
MVP		0.54
MPC		1.3
ClinPred		0.55	D
GERP RS		4.7
Varity_R		0.21
gMVP		0.73

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: chr11-65810081;