12-48107628-A-G

Position:

• chr12-48107628-A-G

Variant summary

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

The NM_001354735.1(PFKM):​c.82+173A>G 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 152,044 control chromosomes in the GnomAD database, including 4,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.23 (4668 hom., cov: 32)
• Consequence: PFKM NM_001354735.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.165

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=-0.8).
• BP6: Variant 12-48107628-A-G is Benign according to our data. Variant chr12-48107628-A-G is described in ClinVar as [Benign]. Clinvar id is 667846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_001166686.2	c.82+173A>G		intron_variant
PFKM	NM_001354735.1	c.82+173A>G		intron_variant
PFKM	NM_001354736.1	c.82+173A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000340802.12	c.82+173A>G		intron_variant		2
PFKM	ENST00000546755.5	c.82+173A>G		intron_variant		4
PFKM	ENST00000548288.5	c.82+173A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34501 AN: 151926 Hom.: 4657 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.234

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: 34539 AN: 152044 Hom.: 4668 Cov.: 32 AF XY: 0.237 AC XY: 17598 AN XY: 74344

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.352

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.230

Alfa AF: 0.180 Hom.: 5025

Bravo AF: 0.239

Asia WGS AF: 0.454 AC: 1574 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10492080; hg19: chr12-48501411;