chr1-59321712-T-C

Position:

• chr1-59321712-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_018291.5(FGGY):​c.163T>C​(p.Ser55Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGGY NM_018291.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGGY	NM_018291.5	c.163T>C	p.Ser55Pro	missense_variant	2/16	ENST00000303721.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGGY	ENST00000303721.12	c.163T>C	p.Ser55Pro	missense_variant	2/16	1	NM_018291.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2023

The c.163T>C (p.S55P) alteration is located in exon 2 (coding exon 1) of the FGGY gene. This alteration results from a T to C substitution at nucleotide position 163, causing the serine (S) at amino acid position 55 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.018	T;.;T;.
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D;D
M_CAP	Benign	0.046	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	.;M;M;M
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D;D;D;T
Sift4G	Pathogenic	0.0010	D;D;D;D
Polyphen		1.0	.;D;D;.
Vest4		0.85, 0.87, 0.95
MutPred		0.66		Loss of glycosylation at S55 (P = 0.0891);Loss of glycosylation at S55 (P = 0.0891);Loss of glycosylation at S55 (P = 0.0891);Loss of glycosylation at S55 (P = 0.0891);
MVP		0.42
MPC		0.22
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.95
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-59787384;