12-48107374-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_001354735.1(PFKM):āc.1A>Gā(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000502 in 1,593,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000049 ( 0 hom. )
Consequence
PFKM
NM_001354735.1 start_lost
NM_001354735.1 start_lost
Scores
2
4
10
Clinical Significance
Conservation
PhyloP100: 2.14
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 3 ACMG points.
PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 33 CDS bases. Genomic position: 48107406. Lost 0.012 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PFKM | NM_001354735.1 | c.1A>G | p.Met1? | start_lost | Exon 2 of 26 | NP_001341664.1 | ||
PFKM | NM_001354736.1 | c.1A>G | p.Met1? | start_lost | Exon 2 of 26 | NP_001341665.1 | ||
PFKM | NM_001166686.2 | c.1A>G | p.Met1? | start_lost | Exon 2 of 25 | NP_001160158.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PFKM | ENST00000642730.1 | c.1A>G | p.Met1? | start_lost | Exon 2 of 26 | ENSP00000496597.1 | ||||
PFKM | ENST00000340802.12 | c.1A>G | p.Met1? | start_lost | Exon 2 of 25 | 2 | ENSP00000345771.6 | |||
PFKM | ENST00000549366.5 | c.1A>G | p.Met1? | start_lost | Exon 2 of 7 | 4 | ENSP00000449622.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000854 AC: 2AN: 234212Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 128240
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GnomAD4 exome AF: 0.00000486 AC: 7AN: 1441072Hom.: 0 Cov.: 27 AF XY: 0.00000279 AC XY: 2AN XY: 717788
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Glycogen storage disease, type VII Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 09, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
.;T;T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Benign
T
PROVEAN
Benign
N;N;N;.;N;N
REVEL
Benign
Sift
Pathogenic
D;D;D;.;D;D
Sift4G
Uncertain
D;D;D;.;D;D
Vest4
MutPred
Gain of catalytic residue at F6 (P = 2e-04);Gain of catalytic residue at F6 (P = 2e-04);Gain of catalytic residue at F6 (P = 2e-04);Gain of catalytic residue at F6 (P = 2e-04);Gain of catalytic residue at F6 (P = 2e-04);Gain of catalytic residue at F6 (P = 2e-04);
MVP
ClinPred
D
GERP RS
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at