chr1-154988299-G-GGC
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_025207.5(FLAD1):c.568_569dupGC(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
Publications
3 publications found
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]
FLAD1 Gene-Disease associations (from GenCC):
- myopathy with abnormal lipid metabolismInheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 VariationId is 224728.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_025207.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FLAD1 | MANE Select | c.568_569dupGC | p.Val191GlnfsTer10 | frameshift | Exon 2 of 7 | NP_079483.3 | |||
| FLAD1 | c.277_278dupGC | p.Val94GlnfsTer10 | frameshift | Exon 3 of 8 | NP_958800.1 | Q8NFF5-2 | |||
| FLAD1 | c.277_278dupGC | p.Val94GlnfsTer10 | frameshift | Exon 3 of 7 | NP_001171820.1 | Q8NFF5-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| FLAD1 | TSL:1 MANE Select | c.568_569dupGC | p.Val191GlnfsTer10 | frameshift | Exon 2 of 7 | ENSP00000292180.3 | Q8NFF5-1 | ||
| FLAD1 | TSL:1 | c.277_278dupGC | p.Val94GlnfsTer10 | frameshift | Exon 3 of 8 | ENSP00000317296.10 | Q8NFF5-2 | ||
| FLAD1 | TSL:1 | c.277_278dupGC | p.Val94GlnfsTer10 | frameshift | Exon 3 of 7 | ENSP00000357417.1 | Q8NFF5-3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727244 show subpopulations
GnomAD4 exome
AF:
AC:
6
AN:
1461890
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
727244
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33480
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
6
AN:
53418
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1112010
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Multiple acyl-CoA dehydrogenase deficiency (1)
1
-
-
Myopathy with abnormal lipid metabolism (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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