rs763995965
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_033409.4(SLC52A3):c.1149G>A(p.Met383Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000613 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
SLC52A3
NM_033409.4 missense
NM_033409.4 missense
Scores
1
6
7
Clinical Significance
Conservation
PhyloP100: 4.08
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.1149G>A | p.Met383Ile | missense_variant | 4/5 | ENST00000645534.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A3 | ENST00000645534.1 | c.1149G>A | p.Met383Ile | missense_variant | 4/5 | NM_033409.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152200Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250512Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135544
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GnomAD4 exome AF: 0.0000636 AC: 93AN: 1461816Hom.: 0 Cov.: 34 AF XY: 0.0000633 AC XY: 46AN XY: 727204
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74352
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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
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 383 of the SLC52A3 protein (p.Met383Ile). This variant is present in population databases (rs763995965, gnomAD 0.008%). 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: 543056). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Polyphen
P;P;B;P;P
Vest4
0.70, 0.56, 0.70
MutPred
Gain of glycosylation at S384 (P = 0.0744);Gain of glycosylation at S384 (P = 0.0744);Gain of glycosylation at S384 (P = 0.0744);Gain of glycosylation at S384 (P = 0.0744);Gain of glycosylation at S384 (P = 0.0744);
MVP
0.78
MPC
0.74
ClinPred
T
GERP RS
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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