Genetic Variant SLC52A3:c.*12A>G (chr20-761014-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_033409.4(SLC52A3):c.*12A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000717 in 1,589,140 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000078 ( 2 hom. )

Consequence

SLC52A3
NM_033409.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.973

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 20-761014-T-C is Benign according to our data. Variant chr20-761014-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 667165.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.0000779 (112/1438012) while in subpopulation AMR AF = 0.00266 (111/41700). AF 95% confidence interval is 0.00226. There are 2 homozygotes in GnomAdExome4. There are 43 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.*12A>G		3_prime_UTR_variant	Exon 5 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.*12A>G		3_prime_UTR_variant	Exon 5 of 5		NM_033409.4	ENSP00000494193.1		Q9NQ40-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000472

AC:

AN:

205294

AF XY:

0.000319

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00314

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000779

AC:

112

AN:

1438012

Hom.:

Cov.:

AF XY:

0.0000603

AC XY:

AN XY:

713642

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32690

American (AMR)

AF:

0.00266

AC:

111

AN:

41700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25754

East Asian (EAS)

AF:

0.00

AC:

AN:

37666

South Asian (SAS)

AF:

0.00

AC:

AN:

82776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50280

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5500

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102196

Other (OTH)

AF:

0.0000168

AC:

AN:

59450

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73784

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41298

American (AMR)

AF:

0.000132

AC:

AN:

15150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5036

South Asian (SAS)

AF:

0.00

AC:

AN:

4736

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67688

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000155

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

c.*12A>G in exon 5 of SLC52A3: This variant is not expected to have clinical sig nificance because it has been identified in 0.63% (26/4114) of Latino chromosome s by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbS NP rs547810606). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.83

(source)

DANN

Benign

0.30

PhyloP100

-0.97

Mutation Taster

=100/0

polymorphism

(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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20-761014-T-C

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