22-30555657-C-T

Variant names:

• chr22-30555657-C-T
• rs138102427
• NM_001318104.2:c.568G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001318104.2(GAL3ST1):​c.568G>A​(p.Gly190Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: GAL3ST1 NM_001318104.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.417
• Publications: 5 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0042194724).

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.568G>A	p.Gly190Ser	missense	Exon 4 of 4	NP_001305033.1	Q99999
	GAL3ST1	NM_001318107.2		c.571G>A	p.Gly191Ser	missense	Exon 4 of 4	NP_001305036.1
	GAL3ST1	NM_001318114.2		c.571G>A	p.Gly191Ser	missense	Exon 3 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.568G>A	p.Gly190Ser	missense	Exon 4 of 4	ENSP00000385207.1	Q99999
	GAL3ST1	ENST00000338911.6	TSL:1	c.568G>A	p.Gly190Ser	missense	Exon 2 of 2	ENSP00000343234.5	Q99999
	GAL3ST1	ENST00000401975.5	TSL:1	c.568G>A	p.Gly190Ser	missense	Exon 4 of 4	ENSP00000384388.1	Q99999

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000324 AC: 81 AN: 250336 AF XY: 0.000317

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00657

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000885

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000168 AC: 246 AN: 1461388 Hom.: 0 Cov.: 33 AF XY: 0.000169 AC XY: 123 AN XY: 727006

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000112 AC: 5 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00689 AC: 180 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000270 AC: 30 AN: 1111992

Other (OTH) AF: 0.000497 AC: 30 AN: 60394

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15 AN XY: 74330

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000287 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000264 AC: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

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	Benign	0.074
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	2.2
DANN	Benign	0.93
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.82	N
PhyloP100		0.42
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.013
Sift	Benign	0.73	T
Sift4G	Benign	0.73	T
Polyphen		0.0020	B
Vest4		0.028
MVP		0.21
MPC		0.72
ClinPred		0.013	T
GERP RS		-3.6
Varity_R		0.030
gMVP		0.40
Mutation Taster		=100/0	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

dbSNP: rs138102427; hg19: chr22-30951644; COSMIC: COSV58892022; COSMIC: COSV58892022;