6-44255273-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_178148.4(SLC35B2):c.732C>A(p.Thr244=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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]

POLR1C (HGNC:):

ACMG classification

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/exons	MANE	UniProt
SLC35B2	NM_178148.4	c.732C>A	p.Thr244=	synonymous_variant	4/4	ENST00000393812.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35B2	ENST00000393812.4	c.732C>A	p.Thr244=	synonymous_variant	4/4	1	NM_178148.4	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24186 AN: 152088 Hom.: 2449 Cov.: 32

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

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.: 33 AF XY: 0.208 AC XY: 151586 AN XY: 727236

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.: 32 AF XY: 0.162 AC XY: 12074 AN XY: 74426

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

Other links and lift over

dbSNP: rs1875324; hg19: chr6-44223010; COSMIC: COSV51489317; COSMIC: COSV51489317;