rs794728004
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_ModeratePP5_Very_Strong
The NM_033409.4(SLC52A3):c.1325_1326del(p.Leu442ArgfsTer64) variant causes a frameshift change. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L442L) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
SLC52A3
NM_033409.4 frameshift
NM_033409.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.14
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 Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0603 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PP5
?
Variant 20-761109-CGA-C is Pathogenic according to our data. Variant chr20-761109-CGA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-761109-CGA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.1325_1326del | p.Leu442ArgfsTer64 | frameshift_variant | 5/5 | ENST00000645534.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A3 | ENST00000645534.1 | c.1325_1326del | p.Leu442ArgfsTer64 | frameshift_variant | 5/5 | NM_033409.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 07, 2020 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 21, 2022 | Frameshift variant predicted to result in protein truncation as the last 28 amino acids are replaced with 63 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26072523, 20206331, 23107375, 34797406) - |
Brown-Vialetto-van Laere syndrome 1 Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | GeneReviews | Mar 17, 2015 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 12, 2010 | - - |
Computational scores
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Calibrated prediction
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Prediction
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