rs139486822

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_033409.4(SLC52A3):c.9C>T(p.Phe3Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,600,526 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0079 ( 8 hom., cov: 31)

Exomes 𝑓: 0.010 ( 113 hom. )

Consequence

SLC52A3
NM_033409.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.48

Publications

2 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 20-765766-G-A is Benign according to our data. Variant chr20-765766-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00791 (1106/139812) while in subpopulation AMR AF = 0.0129 (188/14574). AF 95% confidence interval is 0.0114. There are 8 homozygotes in GnomAd4. There are 517 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.9C>T	p.Phe3Phe	synonymous_variant	Exon 2 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.9C>T	p.Phe3Phe	synonymous_variant	Exon 2 of 5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes

AF:

0.00791

AC:

1105

AN:

139692

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0129

Gnomad ASJ

AF:

0.000886

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000214

Gnomad FIN

AF:

0.00653

Gnomad MID

AF:

0.0129

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.0150

GnomAD2 exomes

AF:

0.00622

AC:

1491

AN:

239864

AF XY:

0.00595

show subpopulations

Gnomad AFR exome

AF:

0.00161

Gnomad AMR exome

AF:

0.00808

Gnomad ASJ exome

AF:

0.000925

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00598

Gnomad NFE exome

AF:

0.00935

Gnomad OTH exome

AF:

0.00981

GnomAD4 exome

AF:

0.0102

AC:

14939

AN:

1460714

Hom.:

113

Cov.:

AF XY:

0.00982

AC XY:

7136

AN XY:

726546

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

33474

American (AMR)

AF:

0.00936

AC:

418

AN:

44646

Ashkenazi Jewish (ASJ)

AF:

0.00169

AC:

AN:

26034

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39684

South Asian (SAS)

AF:

0.000233

AC:

AN:

85946

European-Finnish (FIN)

AF:

0.00738

AC:

392

AN:

53142

Middle Eastern (MID)

AF:

0.00417

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0121

AC:

13477

AN:

1111696

Other (OTH)

AF:

0.00840

AC:

507

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

729

1458

2187

2916

3645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.00791

AC:

1106

AN:

139812

Hom.:

Cov.:

AF XY:

0.00755

AC XY:

517

AN XY:

68510

show subpopulations

African (AFR)

AF:

0.00228

AC:

AN:

36358

American (AMR)

AF:

0.0129

AC:

188

AN:

14574

Ashkenazi Jewish (ASJ)

AF:

0.000886

AC:

AN:

3386

East Asian (EAS)

AF:

0.00

AC:

AN:

4742

South Asian (SAS)

AF:

0.000427

AC:

AN:

4682

European-Finnish (FIN)

AF:

0.00653

AC:

AN:

9794

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0116

AC:

733

AN:

63202

Other (OTH)

AF:

0.0149

AC:

AN:

1950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

120

181

241

301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00872

Hom.:

Bravo

AF:

0.00809

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Oct 10, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 02, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SLC52A3: BP4, BP7, BS1, BS2 -

not specified

Benign:1

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.Phe3Phe in exon 2 of SLC52A3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.94% (566/60078) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs139486822). -

Inborn genetic diseases

Benign:1

Jul 11, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

SLC52A3-related disorder

Benign:1

May 06, 2021

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Progressive bulbar palsy of childhood;C0796274:Brown-Vialetto-van Laere syndrome 1

Benign:1

Jul 19, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.35

CADD

Benign

9.0

(source)

DANN

Benign

0.79

PhyloP100

2.5

PromoterAI

-0.038

Neutral

(source)

Mutation Taster

=93/7

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

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over