Variant 12-48119238-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_001354740.1(PFKM):c.-89G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000334 in 981,918 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0015 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PFKM
NM_001354740.1 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.50

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00155 (236/152266) while in subpopulation AFR AF= 0.00537 (223/41554). AF 95% confidence interval is 0.00479. There are 3 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein
PFKM	NM_001354740.1 linkuse as main transcript	c.-89G>C	5_prime_UTR_variant	1/23	NP_001341669.1
PFKM	XM_047429003.1 linkuse as main transcript	c.-89G>C	5_prime_UTR_variant	1/22	XP_047284959.1
PFKM	NM_001354735.1 linkuse as main transcript	c.301+661G>C	intron_variant		NP_001341664.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
PFKM	ENST00000642730.1 linkuse as main transcript	c.301+661G>C	intron_variant		ENSP00000496597.1	A0A2R8Y891
PFKM	ENST00000550257.7 linkuse as main transcript	c.215-3529G>C	intron_variant	4	ENSP00000447997.3	F8VTQ3
PFKM	ENST00000340802.12 linkuse as main transcript	c.206-3529G>C	intron_variant	2	ENSP00000345771.6	P08237-3

Frequencies

GnomAD3 genomes

AF:

0.00154

AC:

234

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000957

GnomAD4 exome

AF:

0.000111

AC:

AN:

829652

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

383322

show subpopulations

Gnomad4 AFR exome

AF:

0.00521

Gnomad4 AMR exome

AF:

0.00204

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000132

Gnomad4 OTH exome

AF:

0.000257

GnomAD4 genome

AF:

0.00155

AC:

236

AN:

152266

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00537

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000208

Hom.:

Bravo

AF:

0.00157

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glycogen storage disease, type VII

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Dec 21, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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