22-30557308-C-T

Position:

chr22-30557308-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001318104.2(GAL3ST1):c.85G>A(p.Val29Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,613,592 control chromosomes in the GnomAD database, including 78,135 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.32 ( 8059 hom., cov: 33)

Exomes 𝑓: 0.31 ( 70076 hom. )

Consequence

GAL3ST1
NM_001318104.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.52

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048956573).

BP6

Variant 22-30557308-C-T is Benign according to our data. Variant chr22-30557308-C-T is described in ClinVar as [Benign]. Clinvar id is 1230435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAL3ST1	NM_001318104.2 linkuse as main transcript	c.85G>A	p.Val29Met	missense_variant	3/4	ENST00000406361.6	NP_001305033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAL3ST1	ENST00000406361.6 linkuse as main transcript	c.85G>A	p.Val29Met	missense_variant	3/4	2	NM_001318104.2	ENSP00000385207	P1

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49307

AN:

152038

Hom.:

8062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.346

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.313

Gnomad OTH

AF:

0.336

GnomAD3 exomes

AF:

0.303

AC:

76041

AN:

251104

Hom.:

11877

AF XY:

0.300

AC XY:

40779

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.368

Gnomad AMR exome

AF:

0.228

Gnomad ASJ exome

AF:

0.379

Gnomad EAS exome

AF:

0.325

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.338

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.307

AC:

448410

AN:

1461436

Hom.:

70076

Cov.:

AF XY:

0.304

AC XY:

221290

AN XY:

727014

show subpopulations

Gnomad4 AFR exome

AF:

0.371

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.215

Gnomad4 FIN exome

AF:

0.329

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.311

GnomAD4 genome

AF:

0.324

AC:

49314

AN:

152156

Hom.:

8059

Cov.:

AF XY:

0.322

AC XY:

23951

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.362

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.323

Gnomad4 NFE

AF:

0.313

Gnomad4 OTH

AF:

0.331

Alfa

AF:

0.318

Hom.:

19393

Bravo

AF:

0.330

TwinsUK

AF:

0.311

AC:

1155

ALSPAC

AF:

0.313

AC:

1205

ESP6500AA

AF:

0.374

AC:

1647

ESP6500EA

AF:

0.318

AC:

2732

ExAC

AF:

0.306

AC:

37191

Asia WGS

AF:

0.271

AC:

947

AN:

3478

EpiCase

AF:

0.321

EpiControl

AF:

0.327

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 32949544) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

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

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.91

.;.;.;D;.;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaRNN

Benign

0.0049

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

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.55

N;N;N;N;N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.93

P;P;P;P;P;P;P

PrimateAI

Benign

0.41

PROVEAN

Benign

0.16

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.051

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

Sift4G

Uncertain

0.052

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

Polyphen

0.14

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

Vest4

0.098

MPC

0.92

ClinPred

0.020

GERP RS

1.1

Varity_R

0.030

gMVP

0.48

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