dbSNP rs726354: PFKM:c.-10+299G>A (chr12-48106551-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_001354735.1(PFKM):c.-10+299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 209,332 control chromosomes in the GnomAD database, including 6,405 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 0.23 ( 4671 hom., cov: 31)

Exomes 𝑓: 0.22 ( 1734 hom. )

Consequence

PFKM
NM_001354735.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.248

Publications

6 publications found

Variant links:

Genes affected

PFKM (HGNC:8877): (phosphofructokinase, muscle) Three phosphofructokinase isozymes exist in humans: muscle, liver and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Tetramer composition varies depending on tissue type. This gene encodes the muscle-type isozyme. Mutations in this gene have been associated with glycogen storage disease type VII, also known as Tarui disease. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]

PFKM Gene-Disease associations (from GenCC):

glycogen storage disease VII
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, Ambry Genetics

PFKM 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
PFKM	NM_001354735.1 link	c.-10+299G>A	intron_variant	Intron 1 of 25	NP_001341664.1
PFKM	NM_001354736.1 link	c.-10+240G>A	intron_variant	Intron 1 of 25	NP_001341665.1
PFKM	NM_001166686.2 link	c.-10+414G>A	intron_variant	Intron 1 of 24	NP_001160158.1	P08237-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
PFKM	ENST00000642730.1 link	c.-10+299G>A	intron_variant	Intron 1 of 25		ENSP00000496597.1	A0A2R8Y891
PFKM	ENST00000550257.7 link	c.91+414G>A	intron_variant	Intron 1 of 23	4	ENSP00000447997.3	F8VTQ3
PFKM	ENST00000340802.12 link	c.-10+414G>A	intron_variant	Intron 1 of 24	2	ENSP00000345771.6	P08237-3

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34493

AN:

151838

Hom.:

4660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.244

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.201

Gnomad EAS

AF:

0.591

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.234

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.224

AC:

12873

AN:

57374

Hom.:

1734

Cov.:

AF XY:

0.236

AC XY:

7200

AN XY:

30534

show subpopulations

African (AFR)

AF:

0.197

AC:

137

AN:

694

American (AMR)

AF:

0.427

AC:

1511

AN:

3540

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

301

AN:

1470

East Asian (EAS)

AF:

0.586

AC:

714

AN:

1218

South Asian (SAS)

AF:

0.320

AC:

3436

AN:

10732

European-Finnish (FIN)

AF:

0.230

AC:

649

AN:

2824

Middle Eastern (MID)

AF:

0.174

AC:

AN:

184

European-Non Finnish (NFE)

AF:

0.162

AC:

5449

AN:

33654

Other (OTH)

AF:

0.211

AC:

644

AN:

3058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

429

858

1287

1716

2145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<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:

0.227

AC:

34532

AN:

151958

Hom.:

4671

Cov.:

AF XY:

0.237

AC XY:

17582

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.223

AC:

9254

AN:

41424

American (AMR)

AF:

0.364

AC:

5555

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

697

AN:

3464

East Asian (EAS)

AF:

0.590

AC:

3042

AN:

5156

South Asian (SAS)

AF:

0.353

AC:

1695

AN:

4806

European-Finnish (FIN)

AF:

0.234

AC:

2472

AN:

10570

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11071

AN:

67954

Other (OTH)

AF:

0.229

AC:

482

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1265

2529

3794

5058

6323

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.199

Hom.:

519

Bravo

AF:

0.239

Asia WGS

AF:

0.454

AC:

1574

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.4

(source)

DANN

Benign

0.77

PhyloP100

0.25

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over