dbSNP rs2838549: PFKL:c.747+981G>A (chr21-44315002-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002626.6(PFKL):c.747+981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,318 control chromosomes in the GnomAD database, including 578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.084 ( 578 hom., cov: 34)

Exomes 𝑓: 0.038 ( 0 hom. )

Consequence

PFKL
NM_002626.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.30

Publications

8 publications found

Variant links:

Genes affected

PFKL (HGNC:8876): (phosphofructokinase, liver type) This gene encodes the liver (L) subunit of an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

PFKL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002626.6. 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
	PFKL	NM_002626.6	MANE Select	c.747+981G>A		intron	N/A	NP_002617.3
	PFKL	NM_001002021.3		c.897+981G>A		intron	N/A	NP_001002021.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PFKL	ENST00000349048.9	TSL:1 MANE Select	c.747+981G>A		intron	N/A	ENSP00000269848.6	P17858-1
PFKL	ENST00000397961.6	TSL:1	n.*1096+981G>A		intron	N/A	ENSP00000381052.2	F8WEU2
PFKL	ENST00000885166.1		c.814G>A	p.Val272Met	missense	Exon 8 of 23	ENSP00000555225.1

Frequencies

GnomAD3 genomes

AF:

0.0845

AC:

12850

AN:

152148

Hom.:

576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.0648

Gnomad AMR

AF:

0.0666

Gnomad ASJ

AF:

0.0954

Gnomad EAS

AF:

0.00634

Gnomad SAS

AF:

0.0976

Gnomad FIN

AF:

0.0706

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0782

Gnomad OTH

AF:

0.0913

GnomAD4 exome

AF:

0.0385

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.100

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0294

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0845

AC:

12860

AN:

152266

Hom.:

578

Cov.:

AF XY:

0.0839

AC XY:

6244

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.112

AC:

4658

AN:

41538

American (AMR)

AF:

0.0666

AC:

1019

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0954

AC:

331

AN:

3470

East Asian (EAS)

AF:

0.00636

AC:

AN:

5192

South Asian (SAS)

AF:

0.0979

AC:

473

AN:

4830

European-Finnish (FIN)

AF:

0.0706

AC:

750

AN:

10618

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0782

AC:

5319

AN:

68000

Other (OTH)

AF:

0.0903

AC:

191

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

624

1248

1871

2495

3119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0815

Hom.:

580

Bravo

AF:

0.0850

Asia WGS

AF:

0.0500

AC:

175

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.14

(source)

DANN

Benign

0.66

PhyloP100

-6.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over