20-765250-G-C
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_033409.4(SLC52A3):āc.525C>Gā(p.Ser175Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000062 ( 0 hom. )
Consequence
SLC52A3
NM_033409.4 missense
NM_033409.4 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 6.10
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23670116).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.525C>G | p.Ser175Arg | missense_variant | 2/5 | ENST00000645534.1 | NP_212134.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC52A3 | ENST00000645534.1 | c.525C>G | p.Ser175Arg | missense_variant | 2/5 | NM_033409.4 | ENSP00000494193 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727238
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 20, 2020 | The p.S175R variant (also known as c.525C>G), located in coding exon 1 of the SLC52A3 gene, results from a C to G substitution at nucleotide position 525. The serine at codon 175 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Brown-Vialetto-van Laere syndrome 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2021 | This sequence change replaces serine with arginine at codon 175 of the SLC52A3 protein (p.Ser175Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SLC52A3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;T;.;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
.;.;N;N;.
REVEL
Benign
Sift
Benign
.;.;T;T;.
Sift4G
Benign
.;T;T;T;.
Polyphen
P;P;P;P;P
Vest4
0.19, 0.19, 0.20
MutPred
Gain of catalytic residue at S175 (P = 0.0051);Gain of catalytic residue at S175 (P = 0.0051);Gain of catalytic residue at S175 (P = 0.0051);Gain of catalytic residue at S175 (P = 0.0051);Gain of catalytic residue at S175 (P = 0.0051);
MVP
0.71
MPC
0.44
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at