rs2269933

chr12-48133276-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000289.6(PFKM):c.428-39G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,579,568 control chromosomes in the GnomAD database, including 71,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6657 hom., cov: 31)
  • Exomes 𝑓: 0.30 (64942 hom.)
• Consequence: PFKM NM_000289.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-48133276-G-A is Benign according to our data. Variant chr12-48133276-G-A is described in ClinVar as [Benign]. Clinvar id is 255762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_000289.6	c.428-39G>A		intron_variant		ENST00000359794.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000359794.11	c.428-39G>A		intron_variant		1	NM_000289.6	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44455 AN: 151856 Hom.: 6631 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.309

GnomAD3 exomes AF: 0.259 AC: 64859 AN: 250360 Hom.: 8934 AF XY: 0.258 AC XY: 34957 AN XY: 135304

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.273

GnomAD4 exome AF: 0.297 AC: 423500 AN: 1427594 Hom.: 64942 Cov.: 26 AF XY: 0.292 AC XY: 208087 AN XY: 712280

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.233

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.247

Gnomad4 NFE exome AF: 0.317

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.293 AC: 44520 AN: 151974 Hom.: 6657 Cov.: 31 AF XY: 0.287 AC XY: 21342 AN XY: 74286

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.307

Alfa AF: 0.296 Hom.: 3593

Bravo AF: 0.293

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Glycogen storage disease, type VII Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.79
Dann	Benign	0.78

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

Other links and lift over

dbSNP: rs2269933; hg19: chr12-48527059; COSMIC: COSV56656564; COSMIC: COSV56656564;