rs876661313

Positions:

• chr1-154988128-CTTCT-C

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_025207.5(FLAD1):​c.401_404delTTCT​(p.Phe134fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLAD1 NM_025207.5 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 7.61

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 18 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 1-154988128-CTTCT-C is Pathogenic according to our data. Variant chr1-154988128-CTTCT-C is described in ClinVar as [Pathogenic]. Clinvar id is 224732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-154988128-CTTCT-C is described in Lovd as [Pathogenic]. Variant chr1-154988128-CTTCT-C is described in Lovd as [Likely_pathogenic]. Variant chr1-154988128-CTTCT-C is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLAD1	NM_025207.5	c.401_404delTTCT	p.Phe134fs	frameshift_variant	2/7	ENST00000292180.8	NP_079483.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLAD1	ENST00000292180.8	c.401_404delTTCT	p.Phe134fs	frameshift_variant	2/7	1	NM_025207.5	ENSP00000292180.3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Myopathy with abnormal lipid metabolism Pathogenic:2

Pathogenic, criteria provided, single submitter	case-control	Pediatric Metabolic Diseases, Hacettepe University	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jul 02, 2014	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs876661313; hg19: chr1-154960604;