rs3746808

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.321C>T(p.Ala107Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 1,609,184 control chromosomes in the GnomAD database, including 76,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6025 hom., cov: 31)

Exomes 𝑓: 0.31 ( 70011 hom. )

Consequence

SLC52A3
NM_033409.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 2.24

Publications

20 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=-0.52).

BP6

Variant 20-765454-G-A is Benign according to our data. Variant chr20-765454-G-A is described in ClinVar as Benign. ClinVar VariationId is 262233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.321C>T	p.Ala107Ala	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.321C>T	p.Ala107Ala	synonymous_variant	Exon 2 of 5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes

AF:

0.269

AC:

40879

AN:

151932

Hom.:

6014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.161

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.314

Gnomad ASJ

AF:

0.290

Gnomad EAS

AF:

0.225

Gnomad SAS

AF:

0.358

Gnomad FIN

AF:

0.384

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.321

AC:

77035

AN:

240208

AF XY:

0.321

show subpopulations

Gnomad AFR exome

AF:

0.152

Gnomad AMR exome

AF:

0.440

Gnomad ASJ exome

AF:

0.291

Gnomad EAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.306

AC:

446195

AN:

1457132

Hom.:

70011

Cov.:

AF XY:

0.308

AC XY:

223093

AN XY:

724464

show subpopulations

African (AFR)

AF:

0.155

AC:

5181

AN:

33416

American (AMR)

AF:

0.427

AC:

18616

AN:

43616

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

7752

AN:

26028

East Asian (EAS)

AF:

0.219

AC:

8648

AN:

39536

South Asian (SAS)

AF:

0.372

AC:

31868

AN:

85772

European-Finnish (FIN)

AF:

0.372

AC:

19749

AN:

53106

Middle Eastern (MID)

AF:

0.277

AC:

1593

AN:

5760

European-Non Finnish (NFE)

AF:

0.302

AC:

335324

AN:

1109680

Other (OTH)

AF:

0.290

AC:

17464

AN:

60218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

22368

44736

67104

89472

111840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11076

22152

33228

44304

55380

<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:

0.269

AC:

40909

AN:

152052

Hom.:

6025

Cov.:

AF XY:

0.274

AC XY:

20375

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.161

AC:

6686

AN:

41510

American (AMR)

AF:

0.315

AC:

4811

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

1006

AN:

3470

East Asian (EAS)

AF:

0.225

AC:

1165

AN:

5170

South Asian (SAS)

AF:

0.358

AC:

1719

AN:

4800

European-Finnish (FIN)

AF:

0.384

AC:

4057

AN:

10568

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20640

AN:

67950

Other (OTH)

AF:

0.262

AC:

551

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1483

2967

4450

5934

7417

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.288

Hom.:

21839

Bravo

AF:

0.260

Asia WGS

AF:

0.317

AC:

1099

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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.Ala107Ala in exon 2 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 52.10% (4717/9054) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs3746808). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 17, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Brown-Vialetto-van Laere syndrome 1

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Progressive bulbar palsy of childhood

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

-0.52

CADD

Benign

6.6

(source)

DANN

Benign

0.37

PhyloP100

2.2

PromoterAI

-0.010

Neutral

(source)

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