12-48143841-A-G

Position:

• chr12-48143841-A-G

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.1880+27A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 1,576,994 control chromosomes in the GnomAD database, including 511,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (46277 hom., cov: 32)
  • Exomes 𝑓: 0.80 (465680 hom.)
• Consequence: PFKM NM_000289.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0700

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]

PFKM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-48143841-A-G is Benign according to our data. Variant chr12-48143841-A-G is described in ClinVar as [Benign]. Clinvar id is 255754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKM	NM_000289.6	c.1880+27A>G		intron_variant		ENST00000359794.11	NP_000280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000359794.11	c.1880+27A>G		intron_variant		1	NM_000289.6	ENSP00000352842.5

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117609 AN: 152024 Hom.: 46245 Cov.: 32

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.838

Gnomad OTH AF: 0.776

GnomAD3 exomes AF: 0.722 AC: 181457 AN: 251394 Hom.: 68697 AF XY: 0.731 AC XY: 99355 AN XY: 135870

Gnomad AFR exome AF: 0.777

Gnomad AMR exome AF: 0.479

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.413

Gnomad SAS exome AF: 0.671

Gnomad FIN exome AF: 0.758

Gnomad NFE exome AF: 0.837

Gnomad OTH exome AF: 0.759

GnomAD4 exome AF: 0.802 AC: 1142296 AN: 1424852 Hom.: 465680 Cov.: 25 AF XY: 0.799 AC XY: 568188 AN XY: 711166

Gnomad4 AFR exome AF: 0.774

Gnomad4 AMR exome AF: 0.499

Gnomad4 ASJ exome AF: 0.795

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.671

Gnomad4 FIN exome AF: 0.764

Gnomad4 NFE exome AF: 0.843

Gnomad4 OTH exome AF: 0.780

GnomAD4 genome AF: 0.774 AC: 117689 AN: 152142 Hom.: 46277 Cov.: 32 AF XY: 0.764 AC XY: 56820 AN XY: 74364

Gnomad4 AFR AF: 0.777

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.801

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.838

Gnomad4 OTH AF: 0.771

Alfa AF: 0.801 Hom.: 9101

Bravo AF: 0.762

Asia WGS AF: 0.546 AC: 1903 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 21, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This 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. -

Glycogen storage disease, type VII Benign:2

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs4075913; hg19: chr12-48537624;