chr20-763664-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033409.4(SLC52A3):c.907A>G(p.Ile303Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,092 control chromosomes in the GnomAD database, including 9,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I303L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.094 ( 711 hom., cov: 33)

Exomes 𝑓: 0.11 ( 8997 hom. )

Consequence

SLC52A3
NM_033409.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 7.92

Publications

22 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028273165).

BP6

Variant 20-763664-T-C is Benign according to our data. Variant chr20-763664-T-C is described in ClinVar as Benign. ClinVar VariationId is 262241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.907A>G	p.Ile303Val	missense_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.907A>G	p.Ile303Val	missense_variant	Exon 3 of 5		NM_033409.4	ENSP00000494193.1		Q9NQ40-1

Frequencies

GnomAD3 genomes

AF:

0.0940

AC:

14294

AN:

152106

Hom.:

709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0734

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0696

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0880

GnomAD2 exomes

AF:

0.103

AC:

25862

AN:

251384

AF XY:

0.107

show subpopulations

Gnomad AFR exome

AF:

0.0724

Gnomad AMR exome

AF:

0.0606

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.0912

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.109

AC:

158688

AN:

1461868

Hom.:

8997

Cov.:

AF XY:

0.109

AC XY:

79544

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0663

AC:

2219

AN:

33480

American (AMR)

AF:

0.0628

AC:

2810

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

3349

AN:

26136

East Asian (EAS)

AF:

0.100

AC:

3979

AN:

39700

South Asian (SAS)

AF:

0.140

AC:

12116

AN:

86258

European-Finnish (FIN)

AF:

0.112

AC:

6006

AN:

53406

Middle Eastern (MID)

AF:

0.0803

AC:

463

AN:

5768

European-Non Finnish (NFE)

AF:

0.109

AC:

121326

AN:

1112000

Other (OTH)

AF:

0.106

AC:

6420

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

10098

20197

30295

40394

50492

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4448

8896

13344

17792

22240

<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:

0.0940

AC:

14306

AN:

152224

Hom.:

711

Cov.:

AF XY:

0.0938

AC XY:

6982

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0734

AC:

3049

AN:

41558

American (AMR)

AF:

0.0696

AC:

1065

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

424

AN:

3472

East Asian (EAS)

AF:

0.103

AC:

533

AN:

5160

South Asian (SAS)

AF:

0.135

AC:

653

AN:

4824

European-Finnish (FIN)

AF:

0.109

AC:

1155

AN:

10606

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.106

AC:

7200

AN:

67988

Other (OTH)

AF:

0.0900

AC:

190

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

683

1365

2048

2730

3413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<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:

0.103

Hom.:

3805

Bravo

AF:

0.0886

TwinsUK

AF:

0.110

AC:

408

ALSPAC

AF:

0.114

AC:

441

ESP6500AA

AF:

0.0788

AC:

347

ESP6500EA

AF:

0.110

AC:

943

ExAC

AF:

0.105

AC:

12782

Asia WGS

AF:

0.151

AC:

525

AN:

3478

EpiCase

AF:

0.100

EpiControl

AF:

0.0954

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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.Ile303Val in exon 3 of SLC52A3: This variant is not expected to have clinical significance because it has been identified in 13.79% (2277/16510) of South Asia n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs3746802). -

not provided

Benign:2

Aug 01, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22471455) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Mar 30, 2022

Fulgent Genetics, Fulgent Genetics

Significance: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

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0082

T;T;.;T;T

Eigen

Pathogenic

0.68

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.59

.;.;T;.;T

MetaRNN

Benign

0.0028

T;T;T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Pathogenic

3.2

M;M;M;M;M

PhyloP100

7.9

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.85

.;.;N;N;.

REVEL

Uncertain

0.40

Sift

Benign

0.089

.;.;T;T;.

Sift4G

Benign

0.23

.;T;T;T;.

Polyphen

1.0

D;D;D;D;D

Vest4

0.23, 0.28, 0.23

MPC

0.71

ClinPred

0.072

GERP RS

5.0

Varity_R

0.17

gMVP

0.31

Mutation Taster

=96/4

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