Genetic Variant FGGY:p.Val140Leu (chr1-59346351-G-C) – 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_018291.5(FGGY):c.418G>C(p.Val140Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.86

Publications

2 publications found

Variant links:

Genes affected

FGGY (HGNC:25610): (FGGY carbohydrate kinase domain containing) This gene encodes a protein that phosphorylates carbohydrates such as ribulose, ribitol, and L-arabinitol. Genome-wide association studies in some populations have found an association between polymorphisms in this gene and sporadic amyotrophic lateral sclerosis, but studies of other populations have not been able to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

FGGY 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=0.17028028).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGGY	NM_018291.5 link	c.418G>C	p.Val140Leu	missense_variant	Exon 4 of 16	ENST00000303721.12	NP_060761.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGGY	ENST00000303721.12 link	c.418G>C	p.Val140Leu	missense_variant	Exon 4 of 16	1	NM_018291.5	ENSP00000305922.8		Q96C11-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

250942

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33376

American (AMR)

AF:

0.0000224

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4318

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111620

Other (OTH)

AF:

0.00

AC:

AN:

60188

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0093

T;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.17

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M;M

PhyloP100

3.9

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.84

N;N;N

REVEL

Benign

0.078

Sift

Benign

0.20

T;T;T

Sift4G

Benign

0.32

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.14, 0.10

MutPred

0.47

Loss of catalytic residue at V140 (P = 0.0859);Loss of catalytic residue at V140 (P = 0.0859);Loss of catalytic residue at V140 (P = 0.0859);

MVP

0.13

MPC

0.025

ClinPred

0.066

GERP RS

2.6

Varity_R

0.18

gMVP

0.58

Mutation Taster

=80/20

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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1-59346351-G-C

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