rs1060499726

Positions:

• chr9-94605552-GGGCCCCATAA-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_Strong PM2 PP5_Moderate

The NM_000507.4(FBP1):​c.720_729del​(p.Tyr241GlyfsTer33) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FBP1 NM_000507.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.32

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 8 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 15 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-94605552-GGGCCCCATAA-G is Pathogenic according to our data. Variant chr9-94605552-GGGCCCCATAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 403701.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FBP1	NM_000507.4	c.720_729del	p.Tyr241GlyfsTer33	frameshift_variant	6/7	ENST00000375326.9
FBP1	NM_001127628.2	c.720_729del	p.Tyr241GlyfsTer33	frameshift_variant	7/8
FBP1	XM_006717005.5	c.474_483del	p.Tyr159GlyfsTer33	frameshift_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FBP1	ENST00000375326.9	c.720_729del	p.Tyr241GlyfsTer33	frameshift_variant	6/7	1	NM_000507.4	P1
FBP1	ENST00000415431.5	c.720_729del	p.Tyr241GlyfsTer33	frameshift_variant	7/8	2		P1
FBP1	ENST00000648117.1	c.525_534del	p.Tyr176GlyfsTer33	frameshift_variant	5/6
FBP1	ENST00000682520.1	c.*157_*166del		3_prime_UTR_variant, NMD_transcript_variant	6/7

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fructose-biphosphatase deficiency Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center

Mar 27, 2017

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1060499726; hg19: chr9-97367834;