Genetic Variant SLC35B2:p.Thr244Thr (chr6-44255273-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_178148.4(SLC35B2):c.732C>A(p.Thr244Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,614,082 control chromosomes in the GnomAD database, including 36,655 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 0.16 ( 2450 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34205 hom. )

Consequence

SLC35B2
NM_178148.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.74

Publications

30 publications found

Variant links:

Genes affected

SLC35B2 (HGNC:16872): (solute carrier family 35 member B2) Sulfotransferases (e.g., SULT4A1; MIM 608359) use an activated form of sulfate, 3-prime-phosphoadenosine 5-prime-phosphosulfate (PAPS), as a common sulfate donor for sulfation of glycoproteins, proteoglycans, and glycolipids in the endoplasmic reticulum and Golgi apparatus. SLC35B2 is located in the microsomal membrane and transports PAPS from the cytosol, where it is synthesized, into the Golgi lumen (Kamiyama et al., 2003 [PubMed 12716889]).[supplied by OMIM, Mar 2008]

SLC35B2 Gene-Disease associations (from GenCC):

leukodystrophy, hypomyelinating, 26, with chondrodysplasia
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

SLC35B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35B2	NM_178148.4 link	c.732C>A	p.Thr244Thr	synonymous_variant	Exon 4 of 4	ENST00000393812.4	NP_835361.1	Q8TB61-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35B2	ENST00000393812.4 link	c.732C>A	p.Thr244Thr	synonymous_variant	Exon 4 of 4	1	NM_178148.4	ENSP00000377401.3		Q8TB61-1

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24186

AN:

152088

Hom.:

2449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0378

Gnomad AMI

AF:

0.229

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.360

Gnomad SAS

AF:

0.283

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.190

Gnomad OTH

AF:

0.157

GnomAD2 exomes

AF:

0.223

AC:

56069

AN:

251344

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.0324

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.358

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.191

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.207

AC:

302949

AN:

1461876

Hom.:

34205

Cov.:

AF XY:

0.208

AC XY:

151586

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.0306

AC:

1023

AN:

33480

American (AMR)

AF:

0.325

AC:

14516

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.138

AC:

3597

AN:

26136

East Asian (EAS)

AF:

0.418

AC:

16582

AN:

39700

South Asian (SAS)

AF:

0.278

AC:

23944

AN:

86256

European-Finnish (FIN)

AF:

0.178

AC:

9517

AN:

53416

Middle Eastern (MID)

AF:

0.146

AC:

845

AN:

5768

European-Non Finnish (NFE)

AF:

0.199

AC:

221076

AN:

1112000

Other (OTH)

AF:

0.196

AC:

11849

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16329

32658

48988

65317

81646

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8028

16056

24084

32112

40140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.159

AC:

24184

AN:

152206

Hom.:

2450

Cov.:

AF XY:

0.162

AC XY:

12074

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0377

AC:

1568

AN:

41556

American (AMR)

AF:

0.221

AC:

3377

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

474

AN:

3466

East Asian (EAS)

AF:

0.360

AC:

1859

AN:

5164

South Asian (SAS)

AF:

0.283

AC:

1366

AN:

4820

European-Finnish (FIN)

AF:

0.192

AC:

2041

AN:

10608

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.190

AC:

12918

AN:

67982

Other (OTH)

AF:

0.157

AC:

332

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1027

2054

3080

4107

5134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.183

Hom.:

6027

Bravo

AF:

0.158

Asia WGS

AF:

0.302

AC:

1052

AN:

3478

EpiCase

AF:

0.186

EpiControl

AF:

0.188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.4

(source)

DANN

Benign

0.82

PhyloP100

1.7

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over