rs757556

Positions:

• chr12-48108710-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354735.1(PFKM):​c.205+516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,120 control chromosomes in the GnomAD database, including 4,678 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4678 hom., cov: 32)
• Consequence: PFKM NM_001354735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_001166686.2	c.205+516C>T		intron_variant
PFKM	NM_001354735.1	c.205+516C>T		intron_variant
PFKM	NM_001354736.1	c.205+516C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000340802.12	c.205+516C>T		intron_variant		2
PFKM	ENST00000546755.5	c.205+516C>T		intron_variant		4
PFKM	ENST00000548288.5	c.205+516C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34546 AN: 152002 Hom.: 4667 Cov.: 32

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.227 AC: 34584 AN: 152120 Hom.: 4678 Cov.: 32 AF XY: 0.237 AC XY: 17611 AN XY: 74350

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.230

Alfa AF: 0.203 Hom.: 419

Bravo AF: 0.239

Asia WGS AF: 0.451 AC: 1562 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.60

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs757556; hg19: chr12-48502493;