dbSNP rs16992990: SLC52A3:p.Pro200Pro (chr20-763971-G-A) – ACMG Classification: Benign (-21 pts)

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.600C>T(p.Pro200Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00855 in 1,598,728 control chromosomes in the GnomAD database, including 378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 46 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 332 hom. )

Consequence

SLC52A3
NM_033409.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.68

Publications

2 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=-0.89).

BP6

Variant 20-763971-G-A is Benign according to our data. Variant chr20-763971-G-A is described in ClinVar as Benign. ClinVar VariationId is 262236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.68 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.065 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
SLC52A3	NM_033409.4	MANE Select	c.600C>T	p.Pro200Pro	synonymous	Exon 3 of 5	NP_212134.3
SLC52A3	NM_001370085.1		c.600C>T	p.Pro200Pro	synonymous	Exon 4 of 6	NP_001357014.1
SLC52A3	NM_001370086.1		c.600C>T	p.Pro200Pro	synonymous	Exon 4 of 6	NP_001357015.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC52A3	ENST00000645534.1	MANE Select	c.600C>T	p.Pro200Pro	synonymous	Exon 3 of 5	ENSP00000494193.1
SLC52A3	ENST00000217254.11	TSL:5	c.600C>T	p.Pro200Pro	synonymous	Exon 4 of 6	ENSP00000217254.7
SLC52A3	ENST00000488495.3	TSL:3	c.600C>T	p.Pro200Pro	synonymous	Exon 3 of 5	ENSP00000494009.1

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1576

AN:

151746

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00335

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.0432

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00202

Gnomad OTH

AF:

0.0106

GnomAD2 exomes

AF:

0.0174

AC:

3805

AN:

218302

AF XY:

0.0203

show subpopulations

Gnomad AFR exome

AF:

0.0172

Gnomad AMR exome

AF:

0.00317

Gnomad ASJ exome

AF:

0.0360

Gnomad EAS exome

AF:

0.0437

Gnomad FIN exome

AF:

0.000876

Gnomad NFE exome

AF:

0.00306

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00835

AC:

12079

AN:

1446864

Hom.:

332

Cov.:

AF XY:

0.0101

AC XY:

7283

AN XY:

718584

show subpopulations

African (AFR)

AF:

0.0183

AC:

607

AN:

33136

American (AMR)

AF:

0.00300

AC:

124

AN:

41362

Ashkenazi Jewish (ASJ)

AF:

0.0354

AC:

914

AN:

25844

East Asian (EAS)

AF:

0.0344

AC:

1340

AN:

38920

South Asian (SAS)

AF:

0.0683

AC:

5771

AN:

84474

European-Finnish (FIN)

AF:

0.000950

AC:

AN:

52646

Middle Eastern (MID)

AF:

0.0223

AC:

127

AN:

5694

European-Non Finnish (NFE)

AF:

0.00207

AC:

2287

AN:

1104906

Other (OTH)

AF:

0.0143

AC:

859

AN:

59882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

822

1644

2465

3287

4109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

384

576

768

960

<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:

0.0104

AC:

1583

AN:

151864

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

879

AN XY:

74200

show subpopulations

African (AFR)

AF:

0.0160

AC:

662

AN:

41394

American (AMR)

AF:

0.00335

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.0363

AC:

126

AN:

3468

East Asian (EAS)

AF:

0.0425

AC:

218

AN:

5130

South Asian (SAS)

AF:

0.0712

AC:

341

AN:

4788

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00202

AC:

137

AN:

67938

Other (OTH)

AF:

0.0123

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

153

230

306

383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00510

Hom.:

Bravo

AF:

0.00998

Asia WGS

AF:

0.0570

AC:

197

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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.Pro200Pro in exon 3 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 8.23% (1024/12440) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs16992990).

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Aug 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

Benign:1

Jul 30, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Brown-Vialetto-van Laere syndrome 1

Benign:1

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.29

(source)

DANN

Benign

0.35

PhyloP100

-2.7

Mutation Taster

=100/0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over