rs876661310
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_025207.5(FLAD1):c.568_569dup(p.Val191GlnfsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
FLAD1
NM_025207.5 frameshift
NM_025207.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.26
Genes affected
FLAD1 (HGNC:24671): (flavin adenine dinucleotide synthetase 1) This gene encodes the enzyme that catalyzes adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-154988299-G-GGC is Pathogenic according to our data. Variant chr1-154988299-G-GGC is described in ClinVar as [Pathogenic]. Clinvar id is 224728.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLAD1 | NM_025207.5 | c.568_569dup | p.Val191GlnfsTer10 | frameshift_variant | 2/7 | ENST00000292180.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLAD1 | ENST00000292180.8 | c.568_569dup | p.Val191GlnfsTer10 | frameshift_variant | 2/7 | 1 | NM_025207.5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 exome
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6
AN:
1461890
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Cov.:
31
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3
AN XY:
727244
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Multiple acyl-CoA dehydrogenase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Research Unit for Molecular Medicine, Department for Clinical Medicine, Aarhus University | Mar 14, 2016 | - - |
Myopathy with abnormal lipid metabolism Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 10, 2019 | - - |
Computational scores
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Name
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Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at