Genetic Variant SLC35B1:p.Ser255Asn (chr17-49703010-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005827.4(SLC35B1):c.764G>A(p.Ser255Asn) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC35B1
NM_005827.4 missense, splice_region

Scores

Splicing: ADA: 0.01224

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32237098).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35B1	NM_005827.4 link	c.764G>A	p.Ser255Asn	missense_variant, splice_region_variant	Exon 8 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.764G>A	p.Ser255Asn	missense_variant, splice_region_variant	Exon 8 of 9	1	NM_005827.4	ENSP00000240333.8		P78383-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.764G>A (p.S255N) alteration is located in exon 8 (coding exon 8) of the SLC35B1 gene. This alteration results from a G to A substitution at nucleotide position 764, causing the serine (S) at amino acid position 255 to be replaced by an asparagine (N). 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

Benign

0.33

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0097

.;T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

0.011

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

T;T;D

M_CAP

Benign

0.0054

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.39

.;N;.

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.51

.;N;N

REVEL

Benign

0.051

Sift

Benign

0.31

.;T;T

Sift4G

Benign

0.36

.;.;T

Polyphen

0.0050

.;B;.

MutPred

0.27

.;Loss of glycosylation at S255 (P = 0.2162);.;

MVP

0.12

MPC

0.26

ClinPred

0.61

GERP RS

5.2

Varity_R

0.17

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.012

dbscSNV1_RF

Benign

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over