12-48107374-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_001354735.1(PFKM):ā€‹c.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

Scores

2
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.14
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]

Genome browser will be placed here

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
PFKMNM_001354735.1 linkc.1A>G p.Met1? start_lost Exon 2 of 26 NP_001341664.1
PFKMNM_001354736.1 linkc.1A>G p.Met1? start_lost Exon 2 of 26 NP_001341665.1
PFKMNM_001166686.2 linkc.1A>G p.Met1? start_lost 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.1A>G p.Met1? start_lost Exon 2 of 26 ENSP00000496597.1 A0A2R8Y891
PFKMENST00000340802.12 linkc.1A>G p.Met1? start_lost Exon 2 of 25 2 ENSP00000345771.6 P08237-3
PFKMENST00000549366.5 linkc.1A>G p.Met1? start_lost Exon 2 of 7 4 ENSP00000449622.1 F8VVE3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
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:
0.00000854
AC:
2
AN:
234212
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
128240
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000169
GnomAD4 exome
AF:
0.00000486
AC:
7
AN:
1441072
Hom.:
0
Cov.:
27
AF XY:
0.00000279
AC XY:
2
AN XY:
717788
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000362
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74340
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
Alfa
AF:
0.0000480
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000843
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 09, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.032
T
BayesDel_noAF
Benign
-0.11
CADD
Benign
18
DANN
Benign
0.97
DEOGEN2
Benign
0.0053
.;T;T;.;T;.
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.25
FATHMM_MKL
Benign
0.57
D
LIST_S2
Uncertain
0.90
D;D;D;D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.96
D;D;D;D;D;D
MetaSVM
Benign
-0.38
T
PROVEAN
Benign
0.030
N;N;N;.;N;N
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D;D;.;D;D
Sift4G
Uncertain
0.047
D;D;D;.;D;D
Vest4
0.55
MutPred
0.97
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
0.73
ClinPred
0.99
D
GERP RS
2.8
gMVP
0.22

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: rs755094329; hg19: chr12-48501157; API