rs41291967

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000359794.11(PFKM):​c.1500+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,612,842 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 76 hom., cov: 32)
Exomes 𝑓: 0.0065 ( 100 hom. )

Consequence

PFKM
ENST00000359794.11 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.311
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 Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 12-48141859-C-T is Benign according to our data. Variant chr12-48141859-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0194 (2949/152242) while in subpopulation AFR AF= 0.0483 (2007/41540). AF 95% confidence interval is 0.0466. There are 76 homozygotes in gnomad4. There are 1502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PFKMNM_000289.6 linkuse as main transcriptc.1500+32C>T intron_variant ENST00000359794.11 NP_000280.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PFKMENST00000359794.11 linkuse as main transcriptc.1500+32C>T intron_variant 1 NM_000289.6 ENSP00000352842 P1P08237-1

Frequencies

GnomAD3 genomes
AF:
0.0192
AC:
2914
AN:
152124
Hom.:
70
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0476
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.00963
Gnomad ASJ
AF:
0.0325
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.0300
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.00451
Gnomad OTH
AF:
0.0129
GnomAD3 exomes
AF:
0.0109
AC:
2740
AN:
251302
Hom.:
43
AF XY:
0.00982
AC XY:
1334
AN XY:
135828
show subpopulations
Gnomad AFR exome
AF:
0.0498
Gnomad AMR exome
AF:
0.00483
Gnomad ASJ exome
AF:
0.0337
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00477
Gnomad FIN exome
AF:
0.0275
Gnomad NFE exome
AF:
0.00539
Gnomad OTH exome
AF:
0.0111
GnomAD4 exome
AF:
0.00649
AC:
9475
AN:
1460600
Hom.:
100
Cov.:
31
AF XY:
0.00637
AC XY:
4626
AN XY:
726710
show subpopulations
Gnomad4 AFR exome
AF:
0.0479
Gnomad4 AMR exome
AF:
0.00490
Gnomad4 ASJ exome
AF:
0.0344
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00471
Gnomad4 FIN exome
AF:
0.0283
Gnomad4 NFE exome
AF:
0.00364
Gnomad4 OTH exome
AF:
0.0109
GnomAD4 genome
AF:
0.0194
AC:
2949
AN:
152242
Hom.:
76
Cov.:
32
AF XY:
0.0202
AC XY:
1502
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.0483
Gnomad4 AMR
AF:
0.00961
Gnomad4 ASJ
AF:
0.0325
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.0300
Gnomad4 NFE
AF:
0.00451
Gnomad4 OTH
AF:
0.0128
Alfa
AF:
0.0144
Hom.:
4
Bravo
AF:
0.0195
Asia WGS
AF:
0.00953
AC:
33
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 16, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Glycogen storage disease, type VII Benign:1
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesAug 19, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
3.5
DANN
Benign
0.60

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: rs41291967; hg19: chr12-48535642; API