rs3746802

Positions:

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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=0.0028273165).

BP6

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

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/exons	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.907A>G	p.Ile303Val	missense_variant	3/5	ENST00000645534.1	NP_212134.3	Q9NQ40-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1 link	c.907A>G	p.Ile303Val	missense_variant	3/5		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

GnomAD3 exomes

AF:

0.103

AC:

25862

AN:

251384

Hom.:

1454

AF XY:

0.107

AC XY:

14515

AN XY:

135880

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 SAS exome

AF:

0.140

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

Gnomad4 AFR exome

AF:

0.0663

Gnomad4 AMR exome

AF:

0.0628

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.100

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.112

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.106

GnomAD4 genome

AF:

0.0940

AC:

14306

AN:

152224

Hom.:

711

Cov.:

AF XY:

0.0938

AC XY:

6982

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0734

Gnomad4 AMR

AF:

0.0696

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0900

Alfa

AF:

0.103

Hom.:

2094

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Aug 23, 2017	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 01, 2018	This variant is associated with the following publications: (PMID: 22471455) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 30, 2022

- -

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

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.33

CADD

Benign

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

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

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