12-48119244-C-A

Position:

• chr12-48119244-C-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001354740.1(PFKM):​c.-83C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 977,034 control chromosomes in the GnomAD database, including 4,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.060 (356 hom., cov: 31)
  • Exomes 𝑓: 0.090 (3654 hom.)
• Consequence: PFKM NM_001354740.1 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.30

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 12-48119244-C-A is Benign according to our data. Variant chr12-48119244-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 308945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_001354740.1	c.-83C>A		5_prime_UTR_variant	1/23
PFKM	XM_047429003.1	c.-83C>A		5_prime_UTR_variant	1/22
PFKM	NM_001166686.2	c.206-3523C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000340802.12	c.206-3523C>A		intron_variant		2
PFKM	ENST00000546755.5	c.301+667C>A		intron_variant		4
PFKM	ENST00000548288.5	c.206-3523C>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0599 AC: 9104 AN: 151998 Hom.: 356 Cov.: 31

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.0165

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.0839

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.0540

GnomAD4 exome AF: 0.0898 AC: 74107 AN: 824918 Hom.: 3654 Cov.: 20 AF XY: 0.0901 AC XY: 34346 AN XY: 381228

Gnomad4 AFR exome AF: 0.0180

Gnomad4 AMR exome AF: 0.0450

Gnomad4 ASJ exome AF: 0.0179

Gnomad4 EAS exome AF: 0.00248

Gnomad4 SAS exome AF: 0.0157

Gnomad4 FIN exome AF: 0.0616

Gnomad4 NFE exome AF: 0.0948

Gnomad4 OTH exome AF: 0.0705

GnomAD4 genome AF: 0.0599 AC: 9106 AN: 152116 Hom.: 356 Cov.: 31 AF XY: 0.0581 AC XY: 4324 AN XY: 74364

Gnomad4 AFR AF: 0.0245

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.0158

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0839

Gnomad4 NFE AF: 0.0930

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0780 Hom.: 169

Bravo AF: 0.0534

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 12, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Glycogen storage disease, type VII Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	18
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs41291959; hg19: chr12-48513027;