rs3746806

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_033409.4(SLC52A3):c.705C>T(p.Leu235Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,614,156 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L235L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0097 ( 15 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 14 hom. )

Consequence

SLC52A3
NM_033409.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.562

Publications

1 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:

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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=-0.5).

BP6

Variant 20-763866-G-A is Benign according to our data. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763866-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 476614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.562 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00965 (1470/152266) while in subpopulation AFR AF = 0.0333 (1385/41548). AF 95% confidence interval is 0.0319. There are 15 homozygotes in GnomAd4. There are 688 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.705C>T	p.Leu235Leu	synonymous_variant	Exon 3 of 5	ENST00000645534.1	NP_212134.3	Q9NQ40-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1 link	c.705C>T	p.Leu235Leu	synonymous_variant	Exon 3 of 5		NM_033409.4	ENSP00000494193.1		Q9NQ40-1

Frequencies

GnomAD3 genomes

AF:

0.00960

AC:

1460

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0332

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00273

AC:

687

AN:

251366

AF XY:

0.00199

show subpopulations

Gnomad AFR exome

AF:

0.0375

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00102

AC:

1485

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000891

AC XY:

648

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0357

AC:

1195

AN:

33480

American (AMR)

AF:

0.00174

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000139

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000486

AC:

AN:

1112010

Other (OTH)

AF:

0.00215

AC:

130

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

116

232

347

463

579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00965

AC:

1470

AN:

152266

Hom.:

Cov.:

AF XY:

0.00924

AC XY:

688

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0333

AC:

1385

AN:

41548

American (AMR)

AF:

0.00340

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000415

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68012

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

148

223

297

371

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:

0.00368

Hom.:

Bravo

AF:

0.0111

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 16, 2020

GeneDx

Significance:Likely 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

- -

Sep 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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.Leu235Leu 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 3.74% (388/10376) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.br oadinstitute.org; dbSNP rs3746806). -

Brown-Vialetto-van Laere syndrome 1

Benign:1

Feb 02, 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

-0.50

CADD

Benign

4.7

(source)

DANN

Benign

0.56

PhyloP100

0.56

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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