Variant rs193298317 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001354735.1(PFKM):c.53G>A(p.Arg18His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,598,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PFKM
NM_001354735.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.03

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.078220695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
PFKM	NM_001354735.1 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 26	NP_001341664.1
PFKM	NM_001354736.1 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 26	NP_001341665.1
PFKM	NM_001166686.2 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 25	NP_001160158.1	P08237-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
PFKM	ENST00000642730.1 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 26		ENSP00000496597.1	A0A2R8Y891
PFKM	ENST00000340802.12 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 25	2	ENSP00000345771.6	P08237-3
PFKM	ENST00000549366.5 link	c.53G>A	p.Arg18His	missense_variant	Exon 2 of 7	4	ENSP00000449622.1	F8VVE3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000427

AC:

AN:

234234

Hom.:

AF XY:

0.00000780

AC XY:

AN XY:

128252

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000565

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1446216

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719912

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000842

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0084

.;T;T;.;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.68

T;T;T;T;T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.078

T;T;T;T;T;T

MetaSVM

Benign

-0.79

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.050

N;N;N;.;N;N

REVEL

Benign

0.061

Sift

Benign

0.26

T;T;T;.;T;T

Sift4G

Benign

0.090

T;D;D;.;D;D

Vest4

0.23

MutPred

0.43

Gain of catalytic residue at L20 (P = 0.0017);Gain of catalytic residue at L20 (P = 0.0017);Gain of catalytic residue at L20 (P = 0.0017);Gain of catalytic residue at L20 (P = 0.0017);Gain of catalytic residue at L20 (P = 0.0017);Gain of catalytic residue at L20 (P = 0.0017);

MVP

0.64

MPC

0.072

ClinPred

0.93

GERP RS

2.0

gMVP

0.17

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over