Variant 6-8419662-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370476.2(SLC35B3):c.698C>T(p.Ser233Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000262 in 1,527,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

SLC35B3
NM_001370476.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.92

Variant links:

Genes affected

SLC35B3 (HGNC:21601): (solute carrier family 35 member B3) This gene is a member of the solute carrier family. The encoded protein is involved in the transport of 3-prime phosphoadenosine 5-prime phosphosulfate (PAPS) from the nucleus or the cytosol to the Golgi lumen. This gene has been reported to be expressed preferentially in the human colon tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

SLC35B3 links:

SLC35B3 (HGNC:):

SLC35B3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35B3	NM_001370476.2 linkuse as main transcript	c.698C>T	p.Ser233Phe	missense_variant	7/11	ENST00000644923.2	NP_001357405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC35B3	ENST00000644923.2 linkuse as main transcript	c.698C>T	p.Ser233Phe	missense_variant	7/11		NM_001370476.2	ENSP00000496368.1		Q9H1N7-1
SLC35B3	ENST00000710437.1 linkuse as main transcript	c.602C>T	p.Ser201Phe	missense_variant	6/10			ENSP00000518269.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1375336

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

681836

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000518

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151684

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74052

show subpopulations

Gnomad4 AFR

AF:

0.0000485

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2022

The c.698C>T (p.S233F) alteration is located in exon 7 (coding exon 6) of the SLC35B3 gene. This alteration results from a C to T substitution at nucleotide position 698, causing the serine (S) at amino acid position 233 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;.;D

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.9

.;M;M

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.3

.;D;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.012

.;D;.

Sift4G

Uncertain

0.026

.;D;.

Polyphen

0.059

.;B;B

Vest4

0.88

MutPred

0.53

.;Loss of catalytic residue at S233 (P = 0.2494);Loss of catalytic residue at S233 (P = 0.2494);

MVP

0.55

MPC

0.18

ClinPred

0.99

GERP RS

5.4

Varity_R

0.77

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over