9-94584636-C-T

Variant names:

• chr9-94584636-C-T
• NM_003837.4:c.367G>A
• FBP2 p.Gly123Arg

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003837.4(FBP2):​c.367G>A​(p.Gly123Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 14/22 in silico tools predict a damaging 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)
• Consequence: FBP2 NM_003837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.66
• Publications: 0 publications found

Genes affected

FBP2 (HGNC:3607): (fructose-bisphosphatase 2) This gene encodes a gluconeogenesis regulatory enzyme which catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. [provided by RefSeq, Jul 2008]

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

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.994

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003837.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP2	NM_003837.4	MANE Select	c.367G>A	p.Gly123Arg	missense	Exon 3 of 7	NP_003828.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP2	ENST00000375337.4	TSL:1 MANE Select	c.367G>A	p.Gly123Arg	missense	Exon 3 of 7	ENSP00000364486.3	O00757
	PCAT7	ENST00000647389.1		n.1098-2019C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.87	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.91
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.47	D
MetaRNN	Pathogenic	0.99	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.6	H
PhyloP100		7.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Pathogenic	0.98
Sift	Uncertain	0.011	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.92
gMVP		0.96
Mutation Taster		=2/98	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-97346918;