9-94639223-C-T

Position:

• chr9-94639223-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000507.4(FBP1):​c.88G>A​(p.Glu30Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FBP1 NM_000507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.894

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBP1	NM_000507.4	c.88G>A	p.Glu30Lys	missense_variant	1/7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.88G>A	p.Glu30Lys	missense_variant	2/8		NP_001121100.1
FBP1	XM_006717005.5	c.-77+821G>A		intron_variant			XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.88G>A	p.Glu30Lys	missense_variant	1/7	1	NM_000507.4	ENSP00000364475.5
FBP1	ENST00000415431.5	c.88G>A	p.Glu30Lys	missense_variant	2/8	2		ENSP00000408025.1
FBP1	ENST00000414122.1	c.-83+821G>A		intron_variant		5		ENSP00000411619.1
FBP1	ENST00000682520.1	n.88G>A		non_coding_transcript_exon_variant	1/7			ENSP00000507547.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1446924 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 718510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.68	D;D
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Benign	0.65	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.89	D;D
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Pathogenic	3.5	M;M
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.64
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.78	P;P
Vest4		0.68
MutPred		0.71		Gain of MoRF binding (P = 9e-04);Gain of MoRF binding (P = 9e-04);
MVP		0.89
MPC		0.50
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.85
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs121918190; hg19: chr9-97401505; COSMIC: COSV64689288;