NM_001370476.2:c.1057T>C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001370476.2(SLC35B3):c.1057T>C(p.Tyr353His) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000199 in 1,504,724 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

SLC35B3
NM_001370476.2 missense, splice_region

Scores

Splicing: ADA: 0.4799

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.44

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 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
SLC35B3	NM_001370476.2 link	c.1057T>C	p.Tyr353His	missense_variant, splice_region_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.1057T>C	p.Tyr353His	missense_variant, splice_region_variant	Exon 11 of 11		NM_001370476.2	ENSP00000496368.1		Q9H1N7-1
SLC35B3	ENST00000710437.1 link	c.961T>C	p.Tyr321His	missense_variant, splice_region_variant	Exon 10 of 10			ENSP00000518269.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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

GnomAD2 exomes

AF:

0.0000166

AC:

AN:

180824

AF XY:

0.0000102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.39e-7

AC:

AN:

1352574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

672738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28630

American (AMR)

AF:

0.0000314

AC:

AN:

31858

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23358

East Asian (EAS)

AF:

0.00

AC:

AN:

38446

South Asian (SAS)

AF:

0.00

AC:

AN:

75784

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3872

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1046532

Other (OTH)

AF:

0.00

AC:

AN:

56060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.000131

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 27, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1057T>C (p.Y353H) 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 1057, causing the tyrosine (Y) at amino acid position 353 to be replaced by a histidine (H). 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

0.85

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

.;T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;.;D

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.68

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

.;L;L

PhyloP100

8.4

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.1

.;D;.

REVEL

Uncertain

0.47

Sift

Benign

0.25

.;T;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

1.0

.;D;D

Vest4

0.85

MutPred

0.67

.;Loss of stability (P = 0.2336);Loss of stability (P = 0.2336);

MVP

0.49

MPC

0.50

ClinPred

0.83

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.44

gMVP

0.89

Mutation Taster

=15/85

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.48

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_001370476.2:c.1057T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over