NM_000507.4:c.1000A>C

Variant names:

• chr9-94603398-T-G
• NM_000507.4:c.1000A>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_000507.4(FBP1):​c.1000A>C​(p.Lys334Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBP1 NM_000507.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.93
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33675173).
• BP6: Variant 9-94603398-T-G is Benign according to our data. Variant chr9-94603398-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 4023528.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBP1	NM_000507.4	c.1000A>C	p.Lys334Gln	missense_variant	Exon 7 of 7	ENST00000375326.9	NP_000498.2
FBP1	NM_001127628.2	c.1000A>C	p.Lys334Gln	missense_variant	Exon 8 of 8		NP_001121100.1
FBP1	XM_006717005.5	c.754A>C	p.Lys252Gln	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.1000A>C	p.Lys334Gln	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

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Jun 03, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.24	.;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.39	T;.;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.34	T;T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.2	.;M;M
PhyloP100		4.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.1	.;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.064	.;T;T
Sift4G	Uncertain	0.052	.;T;T
Polyphen		0.96	.;D;D
Vest4		0.17, 0.17
MutPred		0.47		.;Loss of ubiquitination at K334 (P = 0.0077);Loss of ubiquitination at K334 (P = 0.0077);
MVP		0.76
MPC		0.32
ClinPred		0.66	D
GERP RS		2.8
Varity_R		0.68
gMVP		0.37
Mutation Taster		=62/38	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

hg19: chr9-97365680;