chr12-48111220-T-C

Variant names:

• chr12-48111220-T-C
• rs11168411
• NM_001354735.1:c.205+3026T>C

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+3026T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0826 in 152,258 control chromosomes in the GnomAD database, including 696 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 0.083 (696 hom., cov: 32)
• Consequence: PFKM NM_001354735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354735.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	NM_001354735.1		c.205+3026T>C		intron	N/A	NP_001341664.1
	PFKM	NM_001354736.1		c.205+3026T>C		intron	N/A	NP_001341665.1
	PFKM	NM_001166686.2		c.205+3026T>C		intron	N/A	NP_001160158.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	ENST00000642730.1		c.205+3026T>C		intron	N/A	ENSP00000496597.1
	PFKM	ENST00000550257.7	TSL:4	c.214+3026T>C		intron	N/A	ENSP00000447997.3
	PFKM	ENST00000340802.12	TSL:2	c.205+3026T>C		intron	N/A	ENSP00000345771.6

Frequencies

GnomAD3 genomes AF: 0.0827 AC: 12575 AN: 152140 Hom.: 696 Cov.: 32

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.0993

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

GnomAD4 genome AF: 0.0826 AC: 12574 AN: 152258 Hom.: 696 Cov.: 32 AF XY: 0.0814 AC XY: 6063 AN XY: 74444

African (AFR) AF: 0.0233 AC: 970 AN: 41568

American (AMR) AF: 0.0667 AC: 1020 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 321 AN: 3460

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0280 AC: 135 AN: 4828

European-Finnish (FIN) AF: 0.134 AC: 1416 AN: 10602

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.123 AC: 8376 AN: 68004

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

Alfa AF: 0.112 Hom.: 1777

Bravo AF: 0.0771

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.61
PhyloP100		0.25
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: rs11168411; hg19: chr12-48505003;