12-48119303-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001354740.1(PFKM):c.-24T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 982,162 control chromosomes in the GnomAD database, including 48,839 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6706 hom., cov: 31)
  • Exomes 𝑓: 0.32 (42133 hom.)
• Consequence: PFKM NM_001354740.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.16

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-48119303-T-G is Benign according to our data. Variant chr12-48119303-T-G is described in ClinVar as [Benign]. Clinvar id is 308946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_001354740.1	c.-24T>G		5_prime_UTR_variant	1/23
PFKM	XM_047429003.1	c.-24T>G		5_prime_UTR_variant	1/22
PFKM	NM_001166686.2	c.206-3464T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000340802.12	c.206-3464T>G		intron_variant		2
PFKM	ENST00000546755.5	c.301+726T>G		intron_variant		4
PFKM	ENST00000548288.5	c.206-3464T>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44624 AN: 151828 Hom.: 6680 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.311

GnomAD4 exome AF: 0.318 AC: 263740 AN: 830216 Hom.: 42133 Cov.: 22 AF XY: 0.317 AC XY: 121749 AN XY: 383488

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.294 AC: 44688 AN: 151946 Hom.: 6706 Cov.: 31 AF XY: 0.288 AC XY: 21422 AN XY: 74258

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.248

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.309

Alfa AF: 0.300 Hom.: 849

Bravo AF: 0.295

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glycogen storage disease, type VII Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.0
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs12306290; hg19: chr12-48513086;