22-30557308-C-G

Variant names:

• chr22-30557308-C-G
• rs2267161
• NM_001318104.2:c.85G>C

Variant summary

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

The NM_001318107.2(GAL3ST1):​c.85G>C​(p.Val29Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V29M) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GAL3ST1 NM_001318107.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 39 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=0.06309897).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318107.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST1	NM_001318104.2	MANE Select	c.85G>C	p.Val29Leu	missense	Exon 3 of 4	NP_001305033.1
	GAL3ST1	NM_001318107.2		c.85G>C	p.Val29Leu	missense	Exon 3 of 4	NP_001305036.1
	GAL3ST1	NM_001318114.2		c.85G>C	p.Val29Leu	missense	Exon 2 of 3	NP_001305043.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAL3ST1	ENST00000406361.6	TSL:2 MANE Select	c.85G>C	p.Val29Leu	missense	Exon 3 of 4	ENSP00000385207.1
	GAL3ST1	ENST00000338911.6	TSL:1	c.85G>C	p.Val29Leu	missense	Exon 1 of 2	ENSP00000343234.5
	GAL3ST1	ENST00000401975.5	TSL:1	c.85G>C	p.Val29Leu	missense	Exon 3 of 4	ENSP00000384388.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.4
DANN	Benign	0.71
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.1	N
PhyloP100		1.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.092
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.55		Loss of loop (P = 0.0235)
MVP		0.15
MPC		0.71
ClinPred		0.044	T
GERP RS		1.1
PromoterAI		0.017	Neutral
Varity_R		0.028
gMVP		0.44
Mutation Taster		=95/5	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: rs2267161; hg19: chr22-30953295;