Variant 22-30556027-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_001318104.2(GAL3ST1):c.198C>G(p.Asn66Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,612,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

GAL3ST1
NM_001318104.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.306

Variant links:

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]

GAL3ST1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity G3ST1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13115227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAL3ST1	NM_001318104.2 linkuse as main transcript	c.198C>G	p.Asn66Lys	missense_variant	4/4	ENST00000406361.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAL3ST1	ENST00000406361.6 linkuse as main transcript	c.198C>G	p.Asn66Lys	missense_variant	4/4	2	NM_001318104.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000766

AC:

AN:

247898

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000550

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:

0.0000157

AC:

AN:

1460484

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000470

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.0000742

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.198C>G (p.N66K) alteration is located in exon 4 (coding exon 2) of the GAL3ST1 gene. This alteration results from a C to G substitution at nucleotide position 198, causing the asparagine (N) at amino acid position 66 to be replaced by a lysine (K). 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

0.18

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.25

DANN

Benign

0.70

DEOGEN2

Benign

0.044

T;T;T;T;T;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.99

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.78

.;.;.;T;.;.;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;M;M;M;M;M;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.87

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.35

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;D;D;D

REVEL

Benign

0.079

Sift

Benign

0.79

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;D

Sift4G

Benign

0.21

T;T;T;T;T;T;T;.;.;.;.;.;T;.;.;.;.;.;.;D;.;.

Polyphen

0.046

B;B;B;B;B;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.14

MutPred

0.60

Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);.;Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);.;Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);.;Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);Gain of ubiquitination at N66 (P = 0.0031);

MVP

0.51

MPC

1.3

ClinPred

0.025

GERP RS

-2.3

Varity_R

0.049

gMVP

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over