chr6-44255273-G-T

Variant names:

• chr6-44255273-G-T
• rs1875324
• NM_178148.4:c.732C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 30 publications found

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: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178148.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35B2	NM_178148.4	MANE Select	c.732C>A	p.Thr244Thr	synonymous	Exon 4 of 4	NP_835361.1	Q8TB61-1
	SLC35B2	NM_001286509.2		c.717C>A	p.Thr239Thr	synonymous	Exon 4 of 4	NP_001273438.1
	SLC35B2	NM_001286510.2		c.717C>A	p.Thr239Thr	synonymous	Exon 4 of 4	NP_001273439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC35B2	ENST00000393812.4	TSL:1 MANE Select	c.732C>A	p.Thr244Thr	synonymous	Exon 4 of 4	ENSP00000377401.3	Q8TB61-1
	SLC35B2	ENST00000615337.4	TSL:4	c.585C>A	p.Thr195Thr	synonymous	Exon 4 of 4	ENSP00000480681.1	Q8TB61-3
	SLC35B2	ENST00000538577.5	TSL:2	c.453C>A	p.Thr151Thr	synonymous	Exon 3 of 3	ENSP00000443845.1	Q8TB61-4

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

GnomAD2 exomes AF: 0.223 AC: 56069 AN: 251344 AF XY: 0.223

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

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

GnomAD4 genome AF: 0.159 AC: 24184 AN: 152206 Hom.: 2450 Cov.: 32 AF XY: 0.162 AC XY: 12074 AN XY: 74426

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: 41 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12918 AN: 67982

Other (OTH) AF: 0.157 AC: 332 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.4
DANN	Benign	0.82
PhyloP100		1.7
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

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