12-48145699-T-G

Position:

chr12-48145699-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000289.6(PFKM):c.2334T>G(p.Ala778Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,613,540 control chromosomes in the GnomAD database, including 106,543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7298 hom., cov: 32)

Exomes 𝑓: 0.36 ( 99245 hom. )

Consequence

PFKM
NM_000289.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12O:1

Conservation

PhyloP100: -0.338

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:

PFKM (HGNC:):

PFKM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 12-48145699-T-G is Benign according to our data. Variant chr12-48145699-T-G is described in ClinVar as [Benign]. Clinvar id is 255758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-48145699-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.338 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKM	NM_000289.6 linkuse as main transcript	c.2334T>G	p.Ala778Ala	synonymous_variant	23/23	ENST00000359794.11	NP_000280.1	P08237-1A0A024R0Y5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000359794.11 linkuse as main transcript	c.2334T>G	p.Ala778Ala	synonymous_variant	23/23	1	NM_000289.6	ENSP00000352842.5		P08237-1

Frequencies

GnomAD3 genomes

AF:

0.286

AC:

43408

AN:

151998

Hom.:

7299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.268

Gnomad ASJ

AF:

0.357

Gnomad EAS

AF:

0.0106

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.370

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.296

GnomAD3 exomes

AF:

0.316

AC:

79487

AN:

251320

Hom.:

14400

AF XY:

0.328

AC XY:

44521

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.238

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.0114

Gnomad SAS exome

AF:

0.374

Gnomad FIN exome

AF:

0.351

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.332

GnomAD4 exome

AF:

0.360

AC:

526152

AN:

1461424

Hom.:

99245

Cov.:

AF XY:

0.361

AC XY:

262772

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.352

Gnomad4 EAS exome

AF:

0.00645

Gnomad4 SAS exome

AF:

0.373

Gnomad4 FIN exome

AF:

0.354

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.332

GnomAD4 genome

AF:

0.285

AC:

43409

AN:

152116

Hom.:

7298

Cov.:

AF XY:

0.284

AC XY:

21092

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.357

Gnomad4 EAS

AF:

0.0108

Gnomad4 SAS

AF:

0.349

Gnomad4 FIN

AF:

0.370

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.366

Hom.:

12457

Bravo

AF:

0.268

Asia WGS

AF:

0.208

AC:

726

AN:

3478

EpiCase

AF:

0.386

EpiControl

AF:

0.379

ClinVar

Significance: Benign

Submissions summary: Benign:12Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease, type VII

Benign:6

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 30, 2023	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2015	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2Other:1

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 21, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.73

DANN

Benign

0.49

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