rs3746803

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033409.4(SLC52A3):c.833C>T(p.Thr278Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,614,094 control chromosomes in the GnomAD database, including 9,591 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.093 ( 700 hom., cov: 33)

Exomes 𝑓: 0.11 ( 8891 hom. )

Consequence

SLC52A3
NM_033409.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.57

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=0.0018212199).

BP6

Variant 20-763738-G-A is Benign according to our data. Variant chr20-763738-G-A is described in ClinVar as [Benign]. Clinvar id is 262240.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-763738-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.833C>T	p.Thr278Met	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.833C>T	p.Thr278Met	missense_variant	Exon 3 of 5		NM_033409.4	ENSP00000494193.1		Q9NQ40-1

Frequencies

GnomAD3 genomes

AF:

0.0931

AC:

14169

AN:

152174

Hom.:

699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0732

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0690

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.0840

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0866

GnomAD3 exomes

AF:

0.101

AC:

25500

AN:

251306

Hom.:

1402

AF XY:

0.105

AC XY:

14308

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0724

Gnomad AMR exome

AF:

0.0603

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.0757

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.101

GnomAD4 exome

AF:

0.108

AC:

157634

AN:

1461802

Hom.:

8891

Cov.:

AF XY:

0.109

AC XY:

79009

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0662

Gnomad4 AMR exome

AF:

0.0626

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.0809

Gnomad4 SAS exome

AF:

0.139

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0931

AC:

14176

AN:

152292

Hom.:

700

Cov.:

AF XY:

0.0928

AC XY:

6908

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0732

Gnomad4 AMR

AF:

0.0691

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.0842

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0862

Alfa

AF:

0.100

Hom.:

1247

Bravo

AF:

0.0878

TwinsUK

AF:

0.110

AC:

407

ALSPAC

AF:

0.114

AC:

440

ESP6500AA

AF:

0.0788

AC:

347

ESP6500EA

AF:

0.110

AC:

943

ExAC

AF:

0.104

AC:

12609

Asia WGS

AF:

0.126

AC:

439

AN:

3478

EpiCase

AF:

0.100

EpiControl

AF:

0.0953

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.Thr278Met in exon 3 of SLC52A3: This variant is not expected to have clinical significance because it has been identified in 13.64% (2253/16512) of South Asia n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstit ute.org; dbSNP rs3746803). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

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

0.066

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0048

T;T;.;T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.50

.;.;T;.;T

MetaRNN

Benign

0.0018

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.29

.;.;N;N;.

REVEL

Benign

0.10

Sift

Benign

0.11

.;.;T;T;.

Sift4G

Benign

0.11

.;T;T;T;.

Polyphen

0.47

P;P;P;P;P

Vest4

0.016, 0.035

MPC

0.34

ClinPred

0.0038

GERP RS

2.4

Varity_R

0.019

gMVP

0.23

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