12-48107081-C-G

Variant names:

• chr12-48107081-C-G
• rs78782922
• NM_001354735.1:c.-9-284C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 rank	MANE	Protein	UniProt
PFKM	NM_001354735.1	c.-9-284C>G		intron_variant	Intron 1 of 25		NP_001341664.1
PFKM	NM_001354736.1	c.-9-284C>G		intron_variant	Intron 1 of 25		NP_001341665.1
PFKM	NM_001166686.2	c.-9-284C>G		intron_variant	Intron 1 of 24		NP_001160158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000642730.1	c.-9-284C>G		intron_variant	Intron 1 of 25			ENSP00000496597.1
PFKM	ENST00000550257.7	c.91+944C>G		intron_variant	Intron 1 of 23	4		ENSP00000447997.3
PFKM	ENST00000340802.12	c.-9-284C>G		intron_variant	Intron 1 of 24	2		ENSP00000345771.6

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

African (AFR) AF: 0.0244 AC: 1013 AN: 41548

American (AMR) AF: 0.0411 AC: 629 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 55 AN: 3472

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.0139 AC: 67 AN: 4820

European-Finnish (FIN) AF: 0.0837 AC: 886 AN: 10582

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0933 AC: 6339 AN: 67978

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

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

Jun 19, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs78782922; hg19: chr12-48500864;