rs910857

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_033409.4(SLC52A3):c.1233T>G(p.Ser411Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000284 in 1,406,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

SLC52A3
NM_033409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC52A3	NM_033409.4 link	c.1233T>G	p.Ser411Arg	missense_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>G	p.Ser411Arg	missense_variant	Exon 5 of 5		NM_033409.4	ENSP00000494193.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

165046

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000769

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:

0.00000284

AC:

AN:

1406300

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694428

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31930

American (AMR)

AF:

0.000108

AC:

AN:

37060

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25262

East Asian (EAS)

AF:

0.00

AC:

AN:

36420

South Asian (SAS)

AF:

0.00

AC:

AN:

80006

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084340

Other (OTH)

AF:

0.00

AC:

AN:

58176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

59234

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Brown-Vialetto-van Laere syndrome 1

Uncertain:1

Jul 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 411 of the SLC52A3 protein (p.Ser411Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLC52A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1463783). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SLC52A3 protein function with a negative predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;T;T;T

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.93

.;.;.;D

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.89

D;D;D;D

MetaSVM

Uncertain

0.48

MutationAssessor

Pathogenic

3.2

M;M;M;M

PhyloP100

1.2

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-4.1

.;.;D;.

REVEL

Pathogenic

0.77

Sift

Uncertain

0.0020

.;.;D;.

Sift4G

Uncertain

0.0020

.;D;D;.

Polyphen

1.0

D;D;D;D

Vest4

0.86, 0.86

MutPred

0.63

Gain of MoRF binding (P = 0.012);Gain of MoRF binding (P = 0.012);Gain of MoRF binding (P = 0.012);Gain of MoRF binding (P = 0.012);

MVP

0.79

MPC

0.53

ClinPred

0.99

GERP RS

4.3

Varity_R

0.62

gMVP

0.95

Mutation Taster

=21/79

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: 1

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over