9-94606869-G-C

Variant names:

• chr9-94606869-G-C
• rs1042144
• NM_000507.4:c.651C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000507.4(FBP1):​c.651C>G​(p.Ala217Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A217A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBP1 NM_000507.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 22 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]

FBP1 Gene-Disease associations (from GenCC):

• fructose-1,6-bisphosphatase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp, Orphanet

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 (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=2.19 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	NM_000507.4	MANE Select	c.651C>G	p.Ala217Ala	synonymous	Exon 5 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.651C>G	p.Ala217Ala	synonymous	Exon 6 of 8	NP_001121100.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	ENST00000375326.9	TSL:1 MANE Select	c.651C>G	p.Ala217Ala	synonymous	Exon 5 of 7	ENSP00000364475.5
	FBP1	ENST00000415431.5	TSL:2	c.651C>G	p.Ala217Ala	synonymous	Exon 6 of 8	ENSP00000408025.1
	FBP1	ENST00000648117.1		c.456C>G	p.Ala152Ala	synonymous	Exon 4 of 6	ENSP00000498145.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 38

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	9.4
DANN	Benign	0.74
PhyloP100		2.2

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

Other links and lift over

dbSNP: rs1042144; hg19: chr9-97369151;