chr9-94603426-G-C

Variant names:

• chr9-94603426-G-C
• rs561592691
• NM_000507.4:c.972C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000507.4(FBP1):​c.972C>G​(p.Asp324Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D324N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBP1 NM_000507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0430
• Publications: 0 publications found

Genes affected

FBP1 (HGNC:3606): (fructose-bisphosphatase 1) Fructose-1,6-bisphosphatase 1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. Fructose-1,6-diphosphatase deficiency is associated with hypoglycemia and metabolic acidosis. [provided by RefSeq, Jul 2008]

PCAT7 (HGNC:48824): (prostate cancer associated transcript 7)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4	c.972C>G	p.Asp324Glu	missense_variant	Exon 7 of 7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.972C>G	p.Asp324Glu	missense_variant	Exon 8 of 8		NP_001121100.1
FBP1	XM_006717005.5	c.726C>G	p.Asp242Glu	missense_variant	Exon 7 of 7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.972C>G	p.Asp324Glu	missense_variant	Exon 7 of 7	1	NM_000507.4	ENSP00000364475.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.45	.;T;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.89
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Pathogenic	0.99	D;.;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.70	D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.1	.;L;L
PhyloP100		-0.043
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.3	.;D;D
REVEL	Uncertain	0.43
Sift	Benign	0.30	.;T;T
Sift4G	Benign	0.45	.;T;T
Polyphen		0.98	.;D;D
Vest4		0.69, 0.68
MutPred		0.55		.;Gain of phosphorylation at S321 (P = 0.3459);Gain of phosphorylation at S321 (P = 0.3459);
MVP		0.77
MPC		0.87
ClinPred		0.94	D
GERP RS		-7.3
Varity_R		0.58
gMVP		0.60
Mutation Taster		=52/48	polymorphism

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

Other links and lift over

dbSNP: rs561592691; hg19: chr9-97365708;