Genetic Variant FLAD1:p.Pro38Ser (chr1-154983806-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025207.5(FLAD1):c.112C>T(p.Pro38Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P38A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FLAD1
NM_025207.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.593

Publications

0 publications found

Variant links:

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 metabolism
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

FLAD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07944715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLAD1	NM_025207.5 link	c.112C>T	p.Pro38Ser	missense_variant	Exon 1 of 7	ENST00000292180.8	NP_079483.3	Q8NFF5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLAD1	ENST00000292180.8 link	c.112C>T	p.Pro38Ser	missense_variant	Exon 1 of 7	1	NM_025207.5	ENSP00000292180.3		Q8NFF5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

T;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.086

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0056

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.81

.;L

PhyloP100

0.59

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.050

Sift

Pathogenic

0.0

D;D

Polyphen

0.0010

.;B

Vest4

0.23

MutPred

0.13

Loss of phosphorylation at T37 (P = 0.0831);Loss of phosphorylation at T37 (P = 0.0831);

MVP

0.20

MPC

0.22

ClinPred

0.076

GERP RS

0.48

PromoterAI

0.0087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.031

gMVP

0.33

Mutation Taster

=100/0

polymorphism

(source)

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

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1-154983806-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over