chr12-48132929-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000289.6(PFKM):​c.299G>C​(p.Arg100Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R100Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

PFKM
NM_000289.6 missense

Scores

2
12
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.594
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PFKMNM_000289.6 linkc.299G>C p.Arg100Pro missense_variant 5/23 ENST00000359794.11 NP_000280.1 P08237-1A0A024R0Y5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PFKMENST00000359794.11 linkc.299G>C p.Arg100Pro missense_variant 5/231 NM_000289.6 ENSP00000352842.5 P08237-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.84
BayesDel_addAF
Uncertain
0.16
D
BayesDel_noAF
Uncertain
-0.010
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.85
D;.;D;.;D;.;D;D;.;.;D;D;D
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.23
FATHMM_MKL
Benign
0.52
D
LIST_S2
Uncertain
0.95
.;D;.;D;.;D;.;.;D;D;D;.;D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.47
T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Uncertain
2.3
M;.;M;.;.;.;M;M;.;M;.;M;M
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.1
D;D;.;D;D;.;D;D;D;D;D;D;D
REVEL
Uncertain
0.60
Sift
Uncertain
0.0050
D;D;.;D;D;.;D;D;D;D;D;D;D
Sift4G
Uncertain
0.014
D;D;.;D;D;.;D;D;D;D;D;D;D
Polyphen
0.21
B;.;B;.;.;.;B;B;.;B;.;B;B
Vest4
0.60, 0.60, 0.60, 0.62, 0.60
MutPred
0.66
Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);.;.;.;Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);
MVP
0.63
MPC
0.86
ClinPred
0.86
D
GERP RS
1.7
Varity_R
0.93
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs2228500; hg19: chr12-48526712; API