Variant chr12-48118502-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBA1

The NM_001354735.1(PFKM):c.226C>A(p.Gln76Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 1,505,510 control chromosomes in the GnomAD database, including 521,697 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.87 ( 57948 hom., cov: 31)

Exomes 𝑓: 0.83 ( 463749 hom. )

Consequence

PFKM
NM_001354735.1 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.437

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PFKM. . Gene score misZ 2.3591 (greater than the threshold 3.09). Trascript score misZ 4.0504 (greater than threshold 3.09). GenCC has associacion of gene with glycogen storage disease VII.

BP4

Computational evidence support a benign effect (MetaRNN=6.907633E-7).

BP6

Variant 12-48118502-C-A is Benign according to our data. Variant chr12-48118502-C-A is described in ClinVar as [Benign]. Clinvar id is 1327006.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-48118502-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
PFKM	NM_001354735.1 linkuse as main transcript	c.226C>A	p.Gln76Lys	missense_variant	4/26
PFKM	NM_001354736.1 linkuse as main transcript	c.226C>A	p.Gln76Lys	missense_variant	4/26
PFKM	XM_047428999.1 linkuse as main transcript	c.436C>A	p.Gln146Lys	missense_variant	4/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL
PFKM	ENST00000642730.1 linkuse as main transcript	c.226C>A	p.Gln76Lys	missense_variant	4/26
PFKM	ENST00000549366.5 linkuse as main transcript	c.226C>A	p.Gln76Lys	missense_variant	4/7	4
PFKM	ENST00000546755.5 linkuse as main transcript	c.226C>A	p.Gln76Lys	missense_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.870

AC:

132255

AN:

152076

Hom.:

57890

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.783

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.834

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.859

Gnomad FIN

AF:

0.829

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.887

GnomAD3 exomes

AF:

0.851

AC:

109039

AN:

128104

Hom.:

46605

AF XY:

0.849

AC XY:

59562

AN XY:

70146

show subpopulations

Gnomad AFR exome

AF:

0.971

Gnomad AMR exome

AF:

0.848

Gnomad ASJ exome

AF:

0.841

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.837

Gnomad FIN exome

AF:

0.841

Gnomad NFE exome

AF:

0.814

Gnomad OTH exome

AF:

0.854

GnomAD4 exome

AF:

0.826

AC:

1118124

AN:

1353316

Hom.:

463749

Cov.:

AF XY:

0.826

AC XY:

553409

AN XY:

669652

show subpopulations

Gnomad4 AFR exome

AF:

0.974

Gnomad4 AMR exome

AF:

0.850

Gnomad4 ASJ exome

AF:

0.835

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.837

Gnomad4 FIN exome

AF:

0.841

Gnomad4 NFE exome

AF:

0.812

Gnomad4 OTH exome

AF:

0.848

GnomAD4 genome

AF:

0.870

AC:

132369

AN:

152194

Hom.:

57948

Cov.:

AF XY:

0.872

AC XY:

64837

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.967

Gnomad4 AMR

AF:

0.859

Gnomad4 ASJ

AF:

0.834

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.858

Gnomad4 FIN

AF:

0.829

Gnomad4 NFE

AF:

0.812

Gnomad4 OTH

AF:

0.888

Alfa

AF:

0.841

Hom.:

12569

Bravo

AF:

0.877

TwinsUK

AF:

0.815

AC:

3023

ALSPAC

AF:

0.813

AC:

3133

ExAC

AF:

0.804

AC:

11526

Asia WGS

AF:

0.942

AC:

3275

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Glycogen storage disease, type VII

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.67

DEOGEN2

Benign

0.011

T;T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.26

T;T;T

MetaRNN

Benign

6.9e-7

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.010

N;N;.

REVEL

Benign

0.098

Sift

Pathogenic

0.0

D;T;.

ClinPred

0.012

GERP RS

0.89

gMVP

0.18

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over