rs11609399

Variant summary

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

The NM_001354735.1(PFKM):​c.5A>C​(p.His2Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H2L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PFKM
NM_001354735.1 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24
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]

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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=0.1918143).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PFKMNM_001354735.1 linkc.5A>C p.His2Pro missense_variant Exon 2 of 26 NP_001341664.1
PFKMNM_001354736.1 linkc.5A>C p.His2Pro missense_variant Exon 2 of 26 NP_001341665.1
PFKMNM_001166686.2 linkc.5A>C p.His2Pro missense_variant Exon 2 of 25 NP_001160158.1 P08237-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PFKMENST00000642730.1 linkc.5A>C p.His2Pro missense_variant Exon 2 of 26 ENSP00000496597.1 A0A2R8Y891
PFKMENST00000340802.12 linkc.5A>C p.His2Pro missense_variant Exon 2 of 25 2 ENSP00000345771.6 P08237-3
PFKMENST00000549366.5 linkc.5A>C p.His2Pro missense_variant Exon 2 of 7 4 ENSP00000449622.1 F8VVE3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.040
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
5.5
DANN
Benign
0.84
DEOGEN2
Benign
0.0059
.;T;T;.;T;.
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.42
T;T;T;T;T;T
M_CAP
Benign
0.058
D
MetaRNN
Benign
0.19
T;T;T;T;T;T
MetaSVM
Benign
-0.50
T
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.12
N;N;N;.;N;N
REVEL
Benign
0.19
Sift
Benign
0.048
D;T;D;.;T;T
Sift4G
Pathogenic
0.0
D;D;D;.;D;D
Vest4
0.36
MutPred
0.29
Gain of catalytic residue at H2 (P = 5e-04);Gain of catalytic residue at H2 (P = 5e-04);Gain of catalytic residue at H2 (P = 5e-04);Gain of catalytic residue at H2 (P = 5e-04);Gain of catalytic residue at H2 (P = 5e-04);Gain of catalytic residue at H2 (P = 5e-04);
MVP
0.52
MPC
0.039
ClinPred
0.25
T
GERP RS
-2.3
gMVP
0.13

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.

Other links and lift over

dbSNP: rs11609399; hg19: chr12-48501161; API