dbSNP rs753319507: FGGY:p.Ala165Gly (chr1-59378777-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_018291.5(FGGY):c.494C>G(p.Ala165Gly) 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 1,461,174 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. A165V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FGGY
NM_018291.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81

Publications

0 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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGGY	NM_018291.5 link	c.494C>G	p.Ala165Gly	missense_variant	Exon 5 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.494C>G	p.Ala165Gly	missense_variant	Exon 5 of 16	1	NM_018291.5	ENSP00000305922.8		Q96C11-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461174

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726892

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111580

Other (OTH)

AF:

0.00

AC:

AN:

60358

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

0.29

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

T;.;T;.

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.58

D;D;D;D

MetaSVM

Benign

-0.44

MutationAssessor

Pathogenic

3.1

.;M;M;.

PhyloP100

2.8

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.012

D;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

0.88, 0.71

.;P;P;.

Vest4

0.67, 0.65, 0.65

MutPred

0.66

Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;

MVP

0.67

MPC

0.20

ClinPred

0.98

GERP RS

4.6

Varity_R

0.85

gMVP

0.70

Mutation Taster

=56/44

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.69

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.69

Position offset: -28

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over