rs11609399

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001354735.1(PFKM):c.5A>T(p.His2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,593,076 control chromosomes in the GnomAD database, including 40,698 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4676 hom., cov: 32)

Exomes 𝑓: 0.20 ( 36022 hom. )

Consequence

PFKM
NM_001354735.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -1.24

Publications

25 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

PFKM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.336159E-5).

BP6

Variant 12-48107378-A-T is Benign according to our data. Variant chr12-48107378-A-T is described in ClinVar as Benign. ClinVar VariationId is 441153.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354735.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PFKM	NM_001354735.1	c.5A>T	p.His2Leu	missense	Exon 2 of 26	NP_001341664.1	A0A2R8Y891
PFKM	NM_001354736.1	c.5A>T	p.His2Leu	missense	Exon 2 of 26	NP_001341665.1	A0A2R8Y891
PFKM	NM_001166686.2	c.5A>T	p.His2Leu	missense	Exon 2 of 25	NP_001160158.1	P08237-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PFKM	ENST00000642730.1		c.5A>T	p.His2Leu	missense	Exon 2 of 26	ENSP00000496597.1	A0A2R8Y891
PFKM	ENST00000340802.12	TSL:2	c.5A>T	p.His2Leu	missense	Exon 2 of 25	ENSP00000345771.6	P08237-3
PFKM	ENST00000549366.5	TSL:4	c.5A>T	p.His2Leu	missense	Exon 2 of 7	ENSP00000449622.1	F8VVE3

Frequencies

GnomAD3 genomes

AF:

0.227

AC:

34536

AN:

152004

Hom.:

4665

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.243

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:

0.146

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.282

AC:

65970

AN:

234192

AF XY:

0.271

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.522

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.243

GnomAD4 exome

AF:

0.198

AC:

284596

AN:

1440954

Hom.:

36022

Cov.:

AF XY:

0.200

AC XY:

143833

AN XY:

717684

show subpopulations

African (AFR)

AF:

0.226

AC:

7531

AN:

33320

American (AMR)

AF:

0.502

AC:

22437

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

5453

AN:

26102

East Asian (EAS)

AF:

0.583

AC:

23106

AN:

39642

South Asian (SAS)

AF:

0.329

AC:

28330

AN:

86094

European-Finnish (FIN)

AF:

0.233

AC:

9107

AN:

39112

Middle Eastern (MID)

AF:

0.174

AC:

998

AN:

5750

European-Non Finnish (NFE)

AF:

0.158

AC:

174444

AN:

1106224

Other (OTH)

AF:

0.220

AC:

13190

AN:

60012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

9425

18850

28275

37700

47125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6654

13308

19962

26616

33270

<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:

34574

AN:

152122

Hom.:

4676

Cov.:

AF XY:

0.237

AC XY:

17606

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.223

AC:

9271

AN:

41498

American (AMR)

AF:

0.364

AC:

5552

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.201

AC:

698

AN:

3468

East Asian (EAS)

AF:

0.590

AC:

3056

AN:

5178

South Asian (SAS)

AF:

0.352

AC:

1698

AN:

4820

European-Finnish (FIN)

AF:

0.234

AC:

2475

AN:

10574

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11075

AN:

67992

Other (OTH)

AF:

0.229

AC:

485

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1295

2590

3885

5180

6475

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:

0.193

Hom.:

2099

Bravo

AF:

0.239

TwinsUK

AF:

0.160

AC:

594

ALSPAC

AF:

0.163

AC:

629

ESP6500AA

AF:

0.228

AC:

714

ESP6500EA

AF:

0.170

AC:

1217

ExAC

AF:

0.266

AC:

31472

Asia WGS

AF:

0.454

AC:

1574

AN:

3478

EpiCase

AF:

0.159

EpiControl

AF:

0.159

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease, type VII (3)

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.36

CADD

Benign

5.3

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.42

MetaRNN

Benign

0.000063

MetaSVM

Benign

-0.92

PhyloP100

-1.2

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.17

REVEL

Benign

0.20

Sift

Benign

0.056

Sift4G

Pathogenic

0.0

Vest4

0.13

MPC

0.038

ClinPred

0.019

GERP RS

-2.3

gMVP

0.17

Mutation Taster

=99/1

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over