Genetic Variant NM_178148.4:c.732C>A (chr6-44255273-G-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.223

AC:

56069

AN:

251344

Hom.:

7306

AF XY:

0.223

AC XY:

30300

AN XY:

135868

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 SAS exome

AF:

0.282

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

Gnomad4 AFR exome

AF:

0.0306

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.418

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.196

GnomAD4 genome

AF:

0.159

AC:

24184

AN:

152206

Hom.:

2450

Cov.:

AF XY:

0.162

AC XY:

12074

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0377

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.360

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.192

Gnomad4 NFE

AF:

0.190

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.185

Hom.:

4561

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

DANN

Benign

0.82

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over