20-761203-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_033409.4(SLC52A3):c.1233T>C(p.Ser411Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 1,558,282 control chromosomes in the GnomAD database, including 397,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35962 hom., cov: 35)

Exomes 𝑓: 0.72 ( 361991 hom. )

Consequence

SLC52A3
NM_033409.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.24

Publications

23 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 20-761203-A-G is Benign according to our data. Variant chr20-761203-A-G is described in ClinVar as Benign. ClinVar VariationId is 262230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.1233T>C	p.Ser411Ser	synonymous_variant	Exon 5 of 5	ENST00000645534.1	NP_212134.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC52A3	ENST00000645534.1 link	c.1233T>C	p.Ser411Ser	synonymous_variant	Exon 5 of 5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes

AF:

0.685

AC:

104196

AN:

152114

Hom.:

35935

Cov.:

show subpopulations

Gnomad AFR

AF:

0.636

Gnomad AMI

AF:

0.778

Gnomad AMR

AF:

0.621

Gnomad ASJ

AF:

0.697

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.739

Gnomad FIN

AF:

0.751

Gnomad MID

AF:

0.718

Gnomad NFE

AF:

0.726

Gnomad OTH

AF:

0.678

GnomAD2 exomes

AF:

0.681

AC:

112365

AN:

165046

AF XY:

0.687

show subpopulations

Gnomad AFR exome

AF:

0.619

Gnomad AMR exome

AF:

0.600

Gnomad ASJ exome

AF:

0.706

Gnomad EAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.733

Gnomad NFE exome

AF:

0.715

Gnomad OTH exome

AF:

0.683

GnomAD4 exome

AF:

0.716

AC:

1006058

AN:

1406048

Hom.:

361991

Cov.:

AF XY:

0.717

AC XY:

497785

AN XY:

694290

show subpopulations

African (AFR)

AF:

0.629

AC:

20085

AN:

31924

American (AMR)

AF:

0.608

AC:

22518

AN:

37034

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

17754

AN:

25262

East Asian (EAS)

AF:

0.473

AC:

17208

AN:

36408

South Asian (SAS)

AF:

0.732

AC:

58585

AN:

80000

European-Finnish (FIN)

AF:

0.737

AC:

35588

AN:

48310

Middle Eastern (MID)

AF:

0.686

AC:

3237

AN:

4722

European-Non Finnish (NFE)

AF:

0.729

AC:

789893

AN:

1084214

Other (OTH)

AF:

0.708

AC:

41190

AN:

58174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

17733

35466

53198

70931

88664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19762

39524

59286

79048

98810

<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:

0.685

AC:

104278

AN:

152234

Hom.:

35962

Cov.:

AF XY:

0.685

AC XY:

50974

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.636

AC:

26444

AN:

41558

American (AMR)

AF:

0.622

AC:

9516

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.697

AC:

2418

AN:

3470

East Asian (EAS)

AF:

0.519

AC:

2675

AN:

5156

South Asian (SAS)

AF:

0.739

AC:

3570

AN:

4830

European-Finnish (FIN)

AF:

0.751

AC:

7967

AN:

10612

Middle Eastern (MID)

AF:

0.724

AC:

213

AN:

294

European-Non Finnish (NFE)

AF:

0.726

AC:

49337

AN:

67990

Other (OTH)

AF:

0.677

AC:

1430

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1761

3522

5284

7045

8806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

820

1640

2460

3280

4100

<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:

0.698

Hom.:

59234

Bravo

AF:

0.673

Asia WGS

AF:

0.609

AC:

2118

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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.Ser411Ser in exon 5 of SLC52A3: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 73.41% (6372/8680) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs910857).

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Brown-Vialetto-van Laere syndrome 1

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Progressive bulbar palsy of childhood

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.2

Mutation Taster

=94/6

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over