dbSNP rs781412205: SLC35B3:p.Leu397Pro (chr6-8413565-A-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001370476.2(SLC35B3):c.1190T>C(p.Leu397Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC35B3
NM_001370476.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.30

Publications

0 publications found

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:

ENSG00000285216 (HGNC:):

ENSG00000285216 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3447159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC35B3	NM_001370476.2 link	c.1190T>C	p.Leu397Pro	missense_variant	Exon 11 of 11	ENST00000644923.2	NP_001357405.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC35B3	ENST00000644923.2 link	c.1190T>C	p.Leu397Pro	missense_variant	Exon 11 of 11		NM_001370476.2	ENSP00000496368.1		Q9H1N7-1
SLC35B3	ENST00000710437.1 link	c.1094T>C	p.Leu365Pro	missense_variant	Exon 10 of 10			ENSP00000518269.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

247926

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457338

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724980

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

44414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

85852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4910

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110410

Other (OTH)

AF:

0.00

AC:

AN:

60110

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1190T>C (p.L397P) alteration is located in exon 11 (coding exon 10) of the SLC35B3 gene. This alteration results from a T to C substitution at nucleotide position 1190, causing the leucine (L) at amino acid position 397 to be replaced by a proline (P). 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

0.20

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

.;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

T;.;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

.;M;M

PhyloP100

6.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

.;N;.

REVEL

Benign

0.089

Sift

Benign

0.085

.;T;.

Sift4G

Uncertain

0.0040

.;D;.

Polyphen

0.98

.;D;D

Vest4

0.43

MutPred

0.29

.;Gain of glycosylation at L397 (P = 0.0266);Gain of glycosylation at L397 (P = 0.0266);

MVP

0.46

MPC

0.33

ClinPred

0.83

GERP RS

5.7

Varity_R

0.38

gMVP

0.95

Mutation Taster

=60/40

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over