rs3746804

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.800C>T(p.Pro267Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,614,056 control chromosomes in the GnomAD database, including 36,953 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P267P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.19 ( 2817 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34136 hom. )

Consequence

SLC52A3
NM_033409.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.337

Publications

39 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: ClinGen, Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
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=0.0032471716).

BP6

Variant 20-763771-G-A is Benign according to our data. Variant chr20-763771-G-A is described in ClinVar as Benign. ClinVar VariationId is 262239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033409.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC52A3	NM_033409.4	MANE Select	c.800C>T	p.Pro267Leu	missense	Exon 3 of 5	NP_212134.3
SLC52A3	NM_001370085.1		c.800C>T	p.Pro267Leu	missense	Exon 4 of 6	NP_001357014.1	Q9NQ40-1
SLC52A3	NM_001370086.1		c.800C>T	p.Pro267Leu	missense	Exon 4 of 6	NP_001357015.1	Q9NQ40-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC52A3	ENST00000645534.1	MANE Select	c.800C>T	p.Pro267Leu	missense	Exon 3 of 5	ENSP00000494193.1	Q9NQ40-1
SLC52A3	ENST00000217254.11	TSL:5	c.800C>T	p.Pro267Leu	missense	Exon 4 of 6	ENSP00000217254.7	Q9NQ40-1
SLC52A3	ENST00000488495.3	TSL:3	c.800C>T	p.Pro267Leu	missense	Exon 3 of 5	ENSP00000494009.1	Q9NQ40-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28517

AN:

152138

Hom.:

2815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.207

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.173

GnomAD2 exomes

AF:

0.195

AC:

49004

AN:

251314

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.184

Gnomad EAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.213

AC:

311303

AN:

1461800

Hom.:

34136

Cov.:

AF XY:

0.213

AC XY:

154644

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.143

AC:

4786

AN:

33480

American (AMR)

AF:

0.117

AC:

5233

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

4836

AN:

26134

East Asian (EAS)

AF:

0.300

AC:

11895

AN:

39696

South Asian (SAS)

AF:

0.199

AC:

17206

AN:

86258

European-Finnish (FIN)

AF:

0.222

AC:

11831

AN:

53408

Middle Eastern (MID)

AF:

0.126

AC:

725

AN:

5768

European-Non Finnish (NFE)

AF:

0.218

AC:

242560

AN:

1111946

Other (OTH)

AF:

0.203

AC:

12231

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17341

34682

52022

69363

86704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8362

16724

25086

33448

41810

<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:

0.188

AC:

28551

AN:

152256

Hom.:

2817

Cov.:

AF XY:

0.187

AC XY:

13891

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.155

AC:

6422

AN:

41544

American (AMR)

AF:

0.149

AC:

2285

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

601

AN:

3468

East Asian (EAS)

AF:

0.269

AC:

1395

AN:

5182

South Asian (SAS)

AF:

0.183

AC:

884

AN:

4826

European-Finnish (FIN)

AF:

0.207

AC:

2200

AN:

10618

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.209

AC:

14228

AN:

68002

Other (OTH)

AF:

0.171

AC:

362

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1213

2426

3640

4853

6066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.204

Hom.:

13476

Bravo

AF:

0.182

TwinsUK

AF:

0.216

AC:

802

ALSPAC

AF:

0.221

AC:

853

ESP6500AA

AF:

0.162

AC:

713

ESP6500EA

AF:

0.214

AC:

1837

ExAC

AF:

0.198

AC:

24056

Asia WGS

AF:

0.251

AC:

875

AN:

3478

EpiCase

AF:

0.197

EpiControl

AF:

0.193

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (2)

Brown-Vialetto-van Laere syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.010

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.34

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.19

REVEL

Benign

0.026

Sift

Benign

0.38

Sift4G

Benign

0.41

Polyphen

0.017

Vest4

0.018

MPC

0.32

ClinPred

0.0018

GERP RS

0.14

Varity_R

0.037

gMVP

0.29

Mutation Taster

=95/5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over