6-44254981-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_178148.4(SLC35B2):c.1024C>G(p.Leu342Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,614,214 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.0037 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (75 hom.)
• Consequence: SLC35B2 NM_178148.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.752

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0075240135).
• BP6: Variant 6-44254981-G-C is Benign according to our data. Variant chr6-44254981-G-C is described in ClinVar as [Benign]. Clinvar id is 781753.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00375 (571/152352) while in subpopulation EAS AF= 0.0317 (164/5180). AF 95% confidence interval is 0.0277. There are 10 homozygotes in gnomad4. There are 318 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC35B2	NM_178148.4	c.1024C>G	p.Leu342Val	missense_variant	4/4	ENST00000393812.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC35B2	ENST00000393812.4	c.1024C>G	p.Leu342Val	missense_variant	4/4	1	NM_178148.4	P1

Frequencies

GnomAD3 genomes AF: 0.00378 AC: 575 AN: 152234 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00685 AC: 1721 AN: 251312 Hom.: 40 AF XY: 0.00595 AC XY: 808 AN XY: 135858

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.0263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0368

Gnomad SAS exome AF: 0.00163

Gnomad FIN exome AF: 0.000693

Gnomad NFE exome AF: 0.000264

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00233 AC: 3410 AN: 1461862 Hom.: 75 Cov.: 30 AF XY: 0.00228 AC XY: 1659 AN XY: 727234

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.0266

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0428

Gnomad4 SAS exome AF: 0.00211

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.0000917

Gnomad4 OTH exome AF: 0.00303

GnomAD4 genome AF: 0.00375 AC: 571 AN: 152352 Hom.: 10 Cov.: 32 AF XY: 0.00427 AC XY: 318 AN XY: 74500

Gnomad4 AFR AF: 0.00127

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0317

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000395 Hom.: 0

Bravo AF: 0.00528

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00611 AC: 742

Asia WGS AF: 0.0150 AC: 53 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	8.4
Dann	Benign	0.82
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.90	D;D;D;.;D
MetaRNN	Benign	0.0075	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.52	T
Sift4G	Benign	1.0	T;T;T;T;T
Polyphen		0.0080	.;.;.;.;B
Vest4		0.081
MVP		0.15
MPC		0.13
ClinPred		0.00034	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.088
gMVP		0.56

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: rs3734707; hg19: chr6-44222718;