chr22-30557334-G-T

Variant names:

• chr22-30557334-G-T
• NM_001318104.2:c.59C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001318104.2(GAL3ST1):​c.59C>A​(p.Ala20Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A20T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GAL3ST1 NM_001318104.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.04
• Publications: 0 publications found

Genes affected

GAL3ST1 (HGNC:24240): (galactose-3-O-sulfotransferase 1) Sulfonation, an important step in the metabolism of many drugs, xenobiotics, hormones, and neurotransmitters, is catalyzed by sulfotransferases. This gene encodes galactosylceramide sulfotransferase, which catalyzes the sulfation of membrane glycolipids including the final step in the synthesis of sulfatide, a major lipid component of the myelin sheath. This gene exhibits elevated expression in ovarian epithelial carcinoma and the encoded enzyme exhibits elevated activity in renal cell carcinoma. Mutations in this gene may be associated with reduced insulin resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318104.2. 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
	GAL3ST1	NM_001318104.2	MANE Select	c.59C>A	p.Ala20Glu	missense	Exon 3 of 4	NP_001305033.1	Q99999
	GAL3ST1	NM_001318107.2		c.59C>A	p.Ala20Glu	missense	Exon 3 of 4	NP_001305036.1
	GAL3ST1	NM_001318114.2		c.59C>A	p.Ala20Glu	missense	Exon 2 of 3	NP_001305043.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST1	ENST00000406361.6	TSL:2 MANE Select	c.59C>A	p.Ala20Glu	missense	Exon 3 of 4	ENSP00000385207.1	Q99999
	GAL3ST1	ENST00000338911.6	TSL:1	c.59C>A	p.Ala20Glu	missense	Exon 1 of 2	ENSP00000343234.5	Q99999
	GAL3ST1	ENST00000401975.5	TSL:1	c.59C>A	p.Ala20Glu	missense	Exon 3 of 4	ENSP00000384388.1	Q99999

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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	0.86
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0081	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.0
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.18
Sift	Uncertain	0.014	D
Sift4G	Benign	0.12	T
Polyphen		0.97	D
Vest4		0.48
MutPred		0.72		Loss of sheet (P = 0.0483)
MVP		0.37
MPC		1.7
ClinPred		0.86	D
GERP RS		3.6
PromoterAI		0.039	Neutral
Varity_R		0.16
gMVP		0.75
Mutation Taster		=85/15	polymorphism

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

hg19: chr22-30953321;