rs3746804

Positions:

chr20-763771-G-A

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 262239.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763771-G-A is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC52A3	NM_033409.4 linkuse as main transcript	c.800C>T	p.Pro267Leu	missense_variant	3/5	ENST00000645534.1	NP_212134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1 linkuse as main transcript	c.800C>T	p.Pro267Leu	missense_variant	3/5		NM_033409.4	ENSP00000494193	P1	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

GnomAD3 exomes

AF:

0.195

AC:

49004

AN:

251314

Hom.:

5155

AF XY:

0.197

AC XY:

26822

AN XY:

135834

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 SAS exome

AF:

0.199

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

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.185

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.222

Gnomad4 NFE exome

AF:

0.218

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.188

AC:

28551

AN:

152256

Hom.:

2817

Cov.:

AF XY:

0.187

AC XY:

13891

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.155

Gnomad4 AMR

AF:

0.149

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.183

Gnomad4 FIN

AF:

0.207

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.202

Hom.:

6695

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

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	p.Pro267Leu in exon 3 of SLC52A3: This variant is not expected to have clinical significance because it has been identified in 26.27% (2264/8618) of East Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs3746804). -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -

Brown-Vialetto-van Laere syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.010

T;T;.;T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.72

.;.;T;.;T

MetaRNN

Benign

0.0032

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.19

.;.;N;N;.

REVEL

Benign

0.026

Sift

Benign

0.38

.;.;T;T;.

Sift4G

Benign

0.41

.;T;T;T;.

Polyphen

0.017

B;B;B;B;B

Vest4

0.018, 0.034

MPC

0.32

ClinPred

0.0018

GERP RS

0.14

Varity_R

0.037

gMVP

0.29

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over