9-94609958-G-T

Position:

• chr9-94609958-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_000507.4(FBP1):​c.530C>A​(p.Ala177Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBP1 NM_000507.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.88

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.947
• PP5: Variant 9-94609958-G-T is Pathogenic according to our data. Variant chr9-94609958-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 869.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FBP1	NM_000507.4	c.530C>A	p.Ala177Asp	missense_variant	4/7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.530C>A	p.Ala177Asp	missense_variant	5/8		NP_001121100.1
FBP1	XM_006717005.5	c.284C>A	p.Ala95Asp	missense_variant	4/7		XP_006717068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FBP1	ENST00000375326.9	c.530C>A	p.Ala177Asp	missense_variant	4/7	1	NM_000507.4	ENSP00000364475	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461880 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Fructose-biphosphatase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 1997

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.68	.;D;D;D
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.98	D;.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.4	.;M;M;.
MutationTaster	Benign	1.0	A;A
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.7	.;N;N;N
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	.;D;D;D
Sift4G	Uncertain	0.0020	.;D;D;D
Polyphen		0.92	.;P;P;.
Vest4		0.96
MutPred		0.84		.;Loss of stability (P = 0.3771);Loss of stability (P = 0.3771);.;
MVP		0.97
MPC		0.71
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.95
gMVP		0.98

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

LitVar

Other links and lift over

dbSNP: rs121918189; hg19: chr9-97372240;