Variant 6-8417484-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001370476.2(SLC35B3):c.791C>T(p.Ser264Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000979 in 1,582,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

SLC35B3
NM_001370476.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC35B3	NM_001370476.2 linkuse as main transcript	c.791C>T	p.Ser264Leu	missense_variant	8/11	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.791C>T	p.Ser264Leu	missense_variant	8/11		NM_001370476.2	ENSP00000496368.1		Q9H1N7-1
SLC35B3	ENST00000710437.1 linkuse as main transcript	c.695C>T	p.Ser232Leu	missense_variant	7/10			ENSP00000518269.1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

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:

0.0000883

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.0000382

AC:

AN:

235324

Hom.:

AF XY:

0.0000471

AC XY:

AN XY:

127412

show subpopulations

Gnomad AFR exome

AF:

0.0000655

Gnomad AMR exome

AF:

0.0000661

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000577

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000470

Gnomad NFE exome

AF:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000944

AC:

135

AN:

1430740

Hom.:

Cov.:

AF XY:

0.0000982

AC XY:

AN XY:

712752

show subpopulations

Gnomad4 AFR exome

AF:

0.0000928

Gnomad4 AMR exome

AF:

0.0000981

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.000169

GnomAD4 genome

AF:

0.000132

AC:

AN:

151826

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000394

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.000949

Alfa

AF:

0.0000580

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.0000247

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3464

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

May 09, 2023

The c.791C>T (p.S264L) alteration is located in exon 8 (coding exon 7) of the SLC35B3 gene. This alteration results from a C to T substitution at nucleotide position 791, causing the serine (S) at amino acid position 264 to be replaced by a leucine (L). 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

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;T;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;.;D

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Benign

-0.89

MutationAssessor

Pathogenic

3.0

.;M;M

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-5.3

.;D;.

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

.;D;.

Sift4G

Pathogenic

0.0010

.;D;.

Polyphen

1.0

.;D;D

Vest4

0.95

MVP

0.71

MPC

0.48

ClinPred

0.85

GERP RS

5.7

Varity_R

0.74

gMVP

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 10

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