Variant 12-48122681-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000312352.11(PFKM):c.-9+4G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,591,546 control chromosomes in the GnomAD database, including 33,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2407 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30808 hom. )

Consequence

PFKM
ENST00000312352.11 splice_donor_region, intron

Scores

Splicing: ADA: 0.004091

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.79

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 12-48122681-G-T is Benign according to our data. Variant chr12-48122681-G-T is described in ClinVar as [Benign]. Clinvar id is 676173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_000289.6 linkuse as main transcript	c.-8-86G>T		intron_variant		ENST00000359794.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000359794.11 linkuse as main transcript	c.-8-86G>T		intron_variant		1	NM_000289.6	P1	P08237-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24995

AN:

152124

Hom.:

2407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0706

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.215

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.203

AC:

291801

AN:

1439304

Hom.:

30808

Cov.:

AF XY:

0.201

AC XY:

143534

AN XY:

714316

show subpopulations

Gnomad4 AFR exome

AF:

0.0653

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.271

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.201

GnomAD4 genome

AF:

0.164

AC:

24990

AN:

152242

Hom.:

2407

Cov.:

AF XY:

0.160

AC XY:

11945

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0705

Gnomad4 AMR

AF:

0.175

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.237

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.215

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.124

Hom.:

274

Bravo

AF:

0.164

Asia WGS

AF:

0.150

AC:

519

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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 16, 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. -

Glycogen storage disease, type VII

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0041

dbscSNV1_RF

Benign

0.036

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over