Genetic Variant SLC35B1:p.Ser91Cys (chr17-49706271-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005827.4(SLC35B1):c.272C>G(p.Ser91Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,556,990 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 23)

Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

SLC35B1
NM_005827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

Variant links:

Genes affected

SLC35B1 (HGNC:20798): (solute carrier family 35 member B1) This gene encodes a nucleotide sugar transporter which is a member of solute carrier family 35. The transporters in this family are highly conserved hydrophobic proteins with multiple transmembrane domains. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

SLC35B1 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
SLC35B1	NM_005827.4 link	c.272C>G	p.Ser91Cys	missense_variant	Exon 3 of 9	ENST00000240333.12	NP_005818.3	P78383-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35B1	ENST00000240333.12 link	c.272C>G	p.Ser91Cys	missense_variant	Exon 3 of 9	1	NM_005827.4	ENSP00000240333.8		P78383-1

Frequencies

GnomAD3 genomes

AF:

0.000409

AC:

AN:

129684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000294

Gnomad ASJ

AF:

0.000296

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000164

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000602

Gnomad OTH

AF:

0.000569

GnomAD3 exomes

AF:

0.000384

AC:

AN:

249884

Hom.:

AF XY:

0.000407

AC XY:

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.000438

Gnomad ASJ exome

AF:

0.000499

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000601

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000556

AC:

794

AN:

1427214

Hom.:

Cov.:

AF XY:

0.000557

AC XY:

395

AN XY:

709324

show subpopulations

Gnomad4 AFR exome

AF:

0.000277

Gnomad4 AMR exome

AF:

0.000532

Gnomad4 ASJ exome

AF:

0.000320

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000668

Gnomad4 OTH exome

AF:

0.000430

GnomAD4 genome

AF:

0.000408

AC:

AN:

129776

Hom.:

Cov.:

AF XY:

0.000361

AC XY:

AN XY:

60970

show subpopulations

Gnomad4 AFR

AF:

0.000233

Gnomad4 AMR

AF:

0.000293

Gnomad4 ASJ

AF:

0.000296

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000164

Gnomad4 NFE

AF:

0.000602

Gnomad4 OTH

AF:

0.000565

Alfa

AF:

0.000610

Hom.:

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000395

AC:

EpiCase

AF:

0.000819

EpiControl

AF:

0.000653

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 21, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.272C>G (p.S91C) alteration is located in exon 3 (coding exon 3) of the SLC35B1 gene. This alteration results from a C to G substitution at nucleotide position 272, causing the serine (S) at amino acid position 91 to be replaced by a cysteine (C). 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

0.69

BayesDel_addAF

Benign

-0.0022

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

.;T;T;T;T;.;.;T

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

D;D;D;D;D;D;D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.50

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.30

MutationAssessor

Pathogenic

3.3

.;M;.;.;.;.;.;.

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.2

.;D;D;D;D;D;D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0030

.;D;D;D;D;D;D;D

Sift4G

Uncertain

0.016

.;.;D;D;.;.;.;.

Polyphen

1.0

.;D;.;.;.;.;.;.

MVP

0.47

MPC

0.95

ClinPred

0.14

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.87

gMVP

0.81

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

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