22-30556027-G-A

Variant names:

• chr22-30556027-G-A
• rs4149493
• NM_001318104.2:c.198C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001318104.2(GAL3ST1):​c.198C>T​(p.Asn66Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000396 in 1,612,822 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00061 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (7 hom.)
• Consequence: GAL3ST1 NM_001318104.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.306
• Publications: 1 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.306 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

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.198C>T	p.Asn66Asn	synonymous	Exon 4 of 4	NP_001305033.1	Q99999
	GAL3ST1	NM_001318107.2		c.201C>T	p.Asn67Asn	synonymous	Exon 4 of 4	NP_001305036.1
	GAL3ST1	NM_001318114.2		c.201C>T	p.Asn67Asn	synonymous	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.198C>T	p.Asn66Asn	synonymous	Exon 4 of 4	ENSP00000385207.1	Q99999
	GAL3ST1	ENST00000338911.6	TSL:1	c.198C>T	p.Asn66Asn	synonymous	Exon 2 of 2	ENSP00000343234.5	Q99999
	GAL3ST1	ENST00000401975.5	TSL:1	c.198C>T	p.Asn66Asn	synonymous	Exon 4 of 4	ENSP00000384388.1	Q99999

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152220 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00121 AC: 300 AN: 247898 AF XY: 0.00106

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0157

Gnomad FIN exome AF: 0.000191

Gnomad NFE exome AF: 0.00000893

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000373 AC: 545 AN: 1460484 Hom.: 7 Cov.: 33 AF XY: 0.000365 AC XY: 265 AN XY: 726582

African (AFR) AF: 0.0000299 AC: 1 AN: 33470

American (AMR) AF: 0.0000671 AC: 3 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0123 AC: 487 AN: 39694

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86250

European-Finnish (FIN) AF: 0.000192 AC: 10 AN: 52206

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

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111888

Other (OTH) AF: 0.000331 AC: 20 AN: 60380

GnomAD4 genome AF: 0.000610 AC: 93 AN: 152338 Hom.: 1 Cov.: 32 AF XY: 0.000779 AC XY: 58 AN XY: 74488

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.000131 AC: 2 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5174

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000820

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		0.31
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: rs4149493; hg19: chr22-30952014;