rs145771944

Variant names:

• chr9-94603533-T-A
• rs145771944
• NM_000507.4:c.865A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PM1 BP4_Strong BP6_Very_Strong BS1

The NM_000507.4(FBP1):​c.865A>T​(p.Met289Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000631 in 1,614,152 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00034 (1 hom.)
• Consequence: FBP1 NM_000507.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.96
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• PM1: In a hotspot region, there are 5 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 1 uncertain in NM_000507.4
• BP4: Computational evidence support a benign effect (MetaRNN=0.01455909).
• BP6: Variant 9-94603533-T-A is Benign according to our data. Variant chr9-94603533-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 214360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00344 (524/152262) while in subpopulation AFR AF = 0.012 (498/41552). AF 95% confidence interval is 0.0111. There are 0 homozygotes in GnomAd4. There are 224 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	NM_000507.4	MANE Select	c.865A>T	p.Met289Leu	missense	Exon 7 of 7	NP_000498.2
	FBP1	NM_001127628.2		c.865A>T	p.Met289Leu	missense	Exon 8 of 8	NP_001121100.1	P09467

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FBP1	ENST00000375326.9	TSL:1 MANE Select	c.865A>T	p.Met289Leu	missense	Exon 7 of 7	ENSP00000364475.5	P09467
	FBP1	ENST00000884868.1		c.1033A>T	p.Met345Leu	missense	Exon 8 of 8	ENSP00000554927.1
	FBP1	ENST00000945615.1		c.1033A>T	p.Met345Leu	missense	Exon 7 of 7	ENSP00000615674.1

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 524 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.000923 AC: 232 AN: 251486 AF XY: 0.000765

Gnomad AFR exome AF: 0.0132

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000338 AC: 494 AN: 1461890 Hom.: 1 Cov.: 35 AF XY: 0.000300 AC XY: 218 AN XY: 727246

African (AFR) AF: 0.0123 AC: 412 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5766

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112010

Other (OTH) AF: 0.000878 AC: 53 AN: 60396

GnomAD4 genome AF: 0.00344 AC: 524 AN: 152262 Hom.: 0 Cov.: 32 AF XY: 0.00301 AC XY: 224 AN XY: 74462

African (AFR) AF: 0.0120 AC: 498 AN: 41552

American (AMR) AF: 0.00124 AC: 19 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.000581 Hom.: 0

Bravo AF: 0.00405

ESP6500AA AF: 0.0102 AC: 45

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00124 AC: 151

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	FBP1-related disorder (1)
-	-	1	Fructose-biphosphatase deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.0
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.077
Sift	Benign	0.15	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.24
MutPred		0.42		Loss of ubiquitination at K291 (P = 0.092)
MVP		0.71
MPC		0.28
ClinPred		0.013	T
GERP RS		4.1
Varity_R		0.39
gMVP		0.46
Mutation Taster		=66/34	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

dbSNP: rs145771944; hg19: chr9-97365815; COSMIC: COSV107478004; COSMIC: COSV107478004;