chr20-761097-T-TGAGCAGCGCTCC
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM4
The NM_033409.4(SLC52A3):c.1338_1339insGGAGCGCTGCTC(p.Gly443_Leu446dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,914 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SLC52A3
NM_033409.4 inframe_insertion
NM_033409.4 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.82
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 Likely_pathogenic. Variant got 6 ACMG points.
PM1
?
In a hotspot region, there are 3 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 4 uncertain in NM_033409.4
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Nonframeshift variant in NON repetitive region in NM_033409.4.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC52A3 | NM_033409.4 | c.1338_1339insGGAGCGCTGCTC | p.Gly443_Leu446dup | inframe_insertion | 5/5 | ENST00000645534.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC52A3 | ENST00000645534.1 | c.1338_1339insGGAGCGCTGCTC | p.Gly443_Leu446dup | inframe_insertion | 5/5 | NM_033409.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1455914Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 723900
GnomAD4 exome
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2
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1455914
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30
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1
AN XY:
723900
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | May 30, 2019 | This variant, c.1327_1338dup, results in the insertion of 4 amino acid(s) to the SLC52A3 protein (p.Gly443_Leu446dup), but otherwise preserves the integrity of the reading frame. 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. This variant has not been reported in the literature in individuals with SLC52A3-related conditions. This variant is not present in population databases (ExAC no frequency). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at