Variant 12-48143846-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000289.6(PFKM):c.1880+32G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,541,192 control chromosomes in the GnomAD database, including 5,807 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 355 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5452 hom. )

Consequence

PFKM
NM_000289.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.967

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-48143846-G-C is Benign according to our data. Variant chr12-48143846-G-C is described in ClinVar as [Benign]. Clinvar id is 255755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0909 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.1880+32G>C		intron_variant		ENST00000359794.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000359794.11 linkuse as main transcript	c.1880+32G>C		intron_variant		1	NM_000289.6	P1	P08237-1

Frequencies

GnomAD3 genomes

AF:

0.0594

AC:

9037

AN:

152170

Hom.:

355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.0158

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0929

Gnomad OTH

AF:

0.0540

GnomAD3 exomes

AF:

0.0572

AC:

14370

AN:

251380

Hom.:

623

AF XY:

0.0573

AC XY:

7782

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.0270

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.0829

Gnomad NFE exome

AF:

0.0906

Gnomad OTH exome

AF:

0.0575

GnomAD4 exome

AF:

0.0816

AC:

113334

AN:

1388904

Hom.:

5452

Cov.:

AF XY:

0.0793

AC XY:

55152

AN XY:

695328

show subpopulations

Gnomad4 AFR exome

AF:

0.0204

Gnomad4 AMR exome

AF:

0.0284

Gnomad4 ASJ exome

AF:

0.0170

Gnomad4 EAS exome

AF:

0.000483

Gnomad4 SAS exome

AF:

0.0162

Gnomad4 FIN exome

AF:

0.0837

Gnomad4 NFE exome

AF:

0.0966

Gnomad4 OTH exome

AF:

0.0690

GnomAD4 genome

AF:

0.0594

AC:

9039

AN:

152288

Hom.:

355

Cov.:

AF XY:

0.0575

AC XY:

4284

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.0369

Gnomad4 ASJ

AF:

0.0158

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0141

Gnomad4 FIN

AF:

0.0839

Gnomad4 NFE

AF:

0.0928

Gnomad4 OTH

AF:

0.0534

Alfa

AF:

0.0716

Hom.:

Bravo

AF:

0.0528

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Glycogen storage disease, type VII

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

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

-0.83

CADD

Benign

6.8

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

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