chr12-48124550-C-A

Variant names:

• chr12-48124550-C-A
• rs11168421
• NM_000289.6:c.85+1691C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000289.6(PFKM):​c.85+1691C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,072 control chromosomes in the GnomAD database, including 6,635 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 0.29 (6635 hom., cov: 32)
• Consequence: PFKM NM_000289.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 6 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 (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PFKM	NM_000289.6	c.85+1691C>A		intron_variant	Intron 2 of 22	ENST00000359794.11	NP_000280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000359794.11	c.85+1691C>A		intron_variant	Intron 2 of 22	1	NM_000289.6	ENSP00000352842.5

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44388 AN: 151954 Hom.: 6609 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.292 AC: 44454 AN: 152072 Hom.: 6635 Cov.: 32 AF XY: 0.287 AC XY: 21306 AN XY: 74336

African (AFR) AF: 0.308 AC: 12762 AN: 41488

American (AMR) AF: 0.253 AC: 3861 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3466

East Asian (EAS) AF: 0.243 AC: 1259 AN: 5172

South Asian (SAS) AF: 0.160 AC: 773 AN: 4818

European-Finnish (FIN) AF: 0.242 AC: 2560 AN: 10560

Middle Eastern (MID) AF: 0.281 AC: 82 AN: 292

European-Non Finnish (NFE) AF: 0.313 AC: 21257 AN: 67968

Other (OTH) AF: 0.309 AC: 652 AN: 2112

Alfa AF: 0.198 Hom.: 549

Bravo AF: 0.293

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.59
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11168421; hg19: chr12-48518333;