12-48107081-C-G

Position:

• chr12-48107081-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001354735.1(PFKM):​c.-9-284C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 152,200 control chromosomes in the GnomAD database, including 361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.060 (361 hom., cov: 32)
• Consequence: PFKM NM_001354735.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.741

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-48107081-C-G is Benign according to our data. Variant chr12-48107081-C-G is described in ClinVar as [Benign]. Clinvar id is 672142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_001166686.2	c.-9-284C>G		intron_variant
PFKM	NM_001354735.1	c.-9-284C>G		intron_variant
PFKM	NM_001354736.1	c.-9-284C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000340802.12	c.-9-284C>G		intron_variant		2
PFKM	ENST00000546755.5	c.-9-284C>G		intron_variant		4
PFKM	ENST00000548288.5	c.-9-284C>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9124 AN: 152082 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.0244

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0411

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0837

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0933

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0600 AC: 9126 AN: 152200 Hom.: 361 Cov.: 32 AF XY: 0.0583 AC XY: 4337 AN XY: 74418

Gnomad4 AFR AF: 0.0244

Gnomad4 AMR AF: 0.0411

Gnomad4 ASJ AF: 0.0158

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.0837

Gnomad4 NFE AF: 0.0933

Gnomad4 OTH AF: 0.0530

Alfa AF: 0.0810 Hom.: 73

Bravo AF: 0.0536

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 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	-0.87
CADD	Benign	3.7
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs78782922; hg19: chr12-48500864;