rs757556

Variant names:

• chr12-48108710-C-T
• rs757556
• NM_001354735.1:c.205+516C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• glycogen storage disease VII

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PFKM	NM_001354735.1	c.205+516C>T		intron_variant	Intron 3 of 25		NP_001341664.1
PFKM	NM_001354736.1	c.205+516C>T		intron_variant	Intron 3 of 25		NP_001341665.1
PFKM	NM_001166686.2	c.205+516C>T		intron_variant	Intron 3 of 24		NP_001160158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000642730.1	c.205+516C>T		intron_variant	Intron 3 of 25			ENSP00000496597.1
PFKM	ENST00000550257.7	c.214+516C>T		intron_variant	Intron 2 of 23	4		ENSP00000447997.3
PFKM	ENST00000340802.12	c.205+516C>T		intron_variant	Intron 3 of 24	2		ENSP00000345771.6

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

African (AFR) AF: 0.223 AC: 9274 AN: 41498

American (AMR) AF: 0.364 AC: 5556 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 698 AN: 3472

East Asian (EAS) AF: 0.590 AC: 3059 AN: 5184

South Asian (SAS) AF: 0.353 AC: 1698 AN: 4816

European-Finnish (FIN) AF: 0.235 AC: 2478 AN: 10564

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11072 AN: 67992

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.204 Hom.: 443

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
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs757556; hg19: chr12-48502493;