chr22-30557275-C-T

Position:

• chr22-30557275-C-T

Variant summary

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

The NM_001318104.2(GAL3ST1):​c.118G>A​(p.Gly40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: GAL3ST1 NM_001318104.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.133

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

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=0.07474849).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAL3ST1	NM_001318104.2	c.118G>A	p.Gly40Ser	missense_variant	3/4	ENST00000406361.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAL3ST1	ENST00000406361.6	c.118G>A	p.Gly40Ser	missense_variant	3/4	2	NM_001318104.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250552 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135410

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461800 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727200

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000180

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.118G>A (p.G40S) alteration is located in exon 3 (coding exon 1) of the GAL3ST1 gene. This alteration results from a G to A substitution at nucleotide position 118, causing the glycine (G) at amino acid position 40 to be replaced by a serine (S). 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	0.063
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.77
DANN	Benign	0.74
DEOGEN2	Benign	0.053	T;T;T;T;T;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.75	.;.;.;T;.;.;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.075	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.52	N;N;N;N;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.44	N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.040
Sift	Benign	0.56	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;T;T;T;T;.;.;.;.;.;T;.;.;.;.;.;.;T;.;.
Polyphen		0.0060	B;B;B;B;B;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.034
MutPred		0.42		Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);Gain of glycosylation at G40 (P = 0.0036);
MVP		0.20
MPC		0.73
ClinPred		0.018	T
GERP RS		-1.5
Varity_R		0.015
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs1299459103; hg19: chr22-30953262;