rs6054605

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033409.4(SLC52A3):c.645C>T(p.Pro215Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,613,664 control chromosomes in the GnomAD database, including 6,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 734 hom., cov: 32)

Exomes 𝑓: 0.064 ( 5777 hom. )

Consequence

SLC52A3
NM_033409.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.72

Publications

10 publications found

Variant links:

Genes affected

SLC52A3 (HGNC:16187): (solute carrier family 52 member 3) This gene encodes a riboflavin transporter protein that is strongly expressed in the intestine and likely plays a role in intestinal absorption of riboflavin. The protein is predicted to have eleven transmembrane domains and a cell surface localization signal in the C-terminus. Mutations at this locus have been associated with Brown-Vialetto-Van Laere syndrome and Fazio-Londe disease. [provided by RefSeq, Mar 2012]

SLC52A3 Gene-Disease associations (from GenCC):

Brown-Vialetto-van Laere syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
progressive bulbar palsy
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

SLC52A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 20-763926-G-A is Benign according to our data. Variant chr20-763926-G-A is described in ClinVar as Benign. ClinVar VariationId is 262237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.645C>T	p.Pro215Pro	synonymous_variant	Exon 3 of 5	ENST00000645534.1	NP_212134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1 link	c.645C>T	p.Pro215Pro	synonymous_variant	Exon 3 of 5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes

AF:

0.0670

AC:

10181

AN:

152024

Hom.:

735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0472

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.0750

Gnomad ASJ

AF:

0.0695

Gnomad EAS

AF:

0.437

Gnomad SAS

AF:

0.0714

Gnomad FIN

AF:

0.0249

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0544

Gnomad OTH

AF:

0.0834

GnomAD2 exomes

AF:

0.0854

AC:

21331

AN:

249854

AF XY:

0.0829

show subpopulations

Gnomad AFR exome

AF:

0.0496

Gnomad AMR exome

AF:

0.0600

Gnomad ASJ exome

AF:

0.0669

Gnomad EAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.0271

Gnomad NFE exome

AF:

0.0577

Gnomad OTH exome

AF:

0.0803

GnomAD4 exome

AF:

0.0637

AC:

93128

AN:

1461522

Hom.:

5777

Cov.:

AF XY:

0.0635

AC XY:

46187

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.0465

AC:

1558

AN:

33476

American (AMR)

AF:

0.0592

AC:

2645

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.0662

AC:

1730

AN:

26130

East Asian (EAS)

AF:

0.393

AC:

15601

AN:

39676

South Asian (SAS)

AF:

0.0548

AC:

4721

AN:

86220

European-Finnish (FIN)

AF:

0.0285

AC:

1521

AN:

53392

Middle Eastern (MID)

AF:

0.0914

AC:

527

AN:

5764

European-Non Finnish (NFE)

AF:

0.0537

AC:

59701

AN:

1111832

Other (OTH)

AF:

0.0849

AC:

5124

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

5528

11056

16585

22113

27641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2392

4784

7176

9568

11960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0669

AC:

10183

AN:

152142

Hom.:

734

Cov.:

AF XY:

0.0689

AC XY:

5126

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0473

AC:

1965

AN:

41504

American (AMR)

AF:

0.0748

AC:

1144

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0695

AC:

241

AN:

3470

East Asian (EAS)

AF:

0.436

AC:

2242

AN:

5138

South Asian (SAS)

AF:

0.0718

AC:

347

AN:

4830

European-Finnish (FIN)

AF:

0.0249

AC:

264

AN:

10610

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0544

AC:

3699

AN:

67992

Other (OTH)

AF:

0.0830

AC:

175

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

461

923

1384

1846

2307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0631

Hom.:

2004

Bravo

AF:

0.0729

Asia WGS

AF:

0.195

AC:

675

AN:

3478

EpiCase

AF:

0.0630

EpiControl

AF:

0.0667

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Pro215Pro in exon 3 of SLC52A3: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 46.21% (3846/8322) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs6054605).

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Brown-Vialetto-van Laere syndrome 1

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.43

(source)

DANN

Benign

0.63

PhyloP100

-4.7

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over