20-765553-G-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.222C>G(p.Ile74Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,577,444 control chromosomes in the GnomAD database, including 6,879 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 390 hom., cov: 31)

Exomes 𝑓: 0.091 ( 6489 hom. )

Consequence

SLC52A3
NM_033409.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.254

Publications

16 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=0.0021209419).

BP6

Variant 20-765553-G-C is Benign according to our data. Variant chr20-765553-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262231.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.222C>G	p.Ile74Met	missense_variant	Exon 2 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.222C>G	p.Ile74Met	missense_variant	Exon 2 of 5		NM_033409.4	ENSP00000494193.1		Q9NQ40-1

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9578

AN:

152122

Hom.:

392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0171

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0441

Gnomad EAS

AF:

0.00789

Gnomad SAS

AF:

0.0289

Gnomad FIN

AF:

0.0664

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0977

Gnomad OTH

AF:

0.0618

GnomAD2 exomes

AF:

0.0648

AC:

12368

AN:

190974

AF XY:

0.0646

show subpopulations

Gnomad AFR exome

AF:

0.0147

Gnomad AMR exome

AF:

0.0423

Gnomad ASJ exome

AF:

0.0510

Gnomad EAS exome

AF:

0.00741

Gnomad FIN exome

AF:

0.0717

Gnomad NFE exome

AF:

0.0980

Gnomad OTH exome

AF:

0.0694

GnomAD4 exome

AF:

0.0909

AC:

129586

AN:

1425206

Hom.:

6489

Cov.:

AF XY:

0.0894

AC XY:

63046

AN XY:

705268

show subpopulations

African (AFR)

AF:

0.0136

AC:

448

AN:

32852

American (AMR)

AF:

0.0436

AC:

1649

AN:

37858

Ashkenazi Jewish (ASJ)

AF:

0.0498

AC:

1263

AN:

25370

East Asian (EAS)

AF:

0.0124

AC:

473

AN:

38128

South Asian (SAS)

AF:

0.0362

AC:

2954

AN:

81610

European-Finnish (FIN)

AF:

0.0766

AC:

3915

AN:

51140

Middle Eastern (MID)

AF:

0.0379

AC:

217

AN:

5720

European-Non Finnish (NFE)

AF:

0.104

AC:

114116

AN:

1093436

Other (OTH)

AF:

0.0770

AC:

4551

AN:

59092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

8100

16201

24301

32402

40502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4108

8216

12324

16432

20540

<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:

0.0629

AC:

9572

AN:

152238

Hom.:

390

Cov.:

AF XY:

0.0602

AC XY:

4484

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0171

AC:

709

AN:

41548

American (AMR)

AF:

0.0605

AC:

926

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0441

AC:

153

AN:

3472

East Asian (EAS)

AF:

0.00791

AC:

AN:

5182

South Asian (SAS)

AF:

0.0281

AC:

135

AN:

4812

European-Finnish (FIN)

AF:

0.0664

AC:

705

AN:

10616

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0977

AC:

6641

AN:

67998

Other (OTH)

AF:

0.0611

AC:

129

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

459

918

1376

1835

2294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<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:

0.0870

Hom.:

457

Bravo

AF:

0.0600

TwinsUK

AF:

0.103

AC:

382

ALSPAC

AF:

0.103

AC:

398

ESP6500AA

AF:

0.0189

AC:

ESP6500EA

AF:

0.0955

AC:

820

ExAC

AF:

0.0540

AC:

6484

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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.Ile74Met in exon 2 of SLC52A3: This variant is not expected to have clinical s ignificance because it has been identified in 12.83% (3040/23690) of European ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs35655964). -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Brown-Vialetto-van Laere syndrome 1

Benign:1

Feb 04, 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

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0059

T;T;.;T;T

Eigen

Benign

0.032

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.68

.;.;T;.;T

MetaRNN

Benign

0.0021

T;T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.4

L;L;L;L;L

PhyloP100

0.25

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

.;.;N;N;.

REVEL

Benign

0.26

Sift

Benign

0.092

.;.;T;T;.

Sift4G

Benign

0.090

.;T;T;T;.

Polyphen

0.89

P;P;P;P;P

Vest4

0.088, 0.10

MPC

0.35

ClinPred

0.022

GERP RS

2.7

PromoterAI

0.019

Neutral

(source)

Varity_R

0.086

gMVP

0.52

Mutation Taster

=84/16

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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