Variant rs41291967 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000359794.11(PFKM):c.1500+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,612,842 control chromosomes in the GnomAD database, including 176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 76 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 100 hom. )

Consequence

PFKM
ENST00000359794.11 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.311

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-48141859-C-T is Benign according to our data. Variant chr12-48141859-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255751.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0194 (2949/152242) while in subpopulation AFR AF= 0.0483 (2007/41540). AF 95% confidence interval is 0.0466. There are 76 homozygotes in gnomad4. There are 1502 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKM	NM_000289.6 linkuse as main transcript	c.1500+32C>T		intron_variant		ENST00000359794.11	NP_000280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000359794.11 linkuse as main transcript	c.1500+32C>T		intron_variant		1	NM_000289.6	ENSP00000352842	P1	P08237-1

Frequencies

GnomAD3 genomes

AF:

0.0192

AC:

2914

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0476

Gnomad AMI

AF:

0.00768

Gnomad AMR

AF:

0.00963

Gnomad ASJ

AF:

0.0325

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.0300

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0109

AC:

2740

AN:

251302

Hom.:

AF XY:

0.00982

AC XY:

1334

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0498

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.0337

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00477

Gnomad FIN exome

AF:

0.0275

Gnomad NFE exome

AF:

0.00539

Gnomad OTH exome

AF:

0.0111

GnomAD4 exome

AF:

0.00649

AC:

9475

AN:

1460600

Hom.:

100

Cov.:

AF XY:

0.00637

AC XY:

4626

AN XY:

726710

show subpopulations

Gnomad4 AFR exome

AF:

0.0479

Gnomad4 AMR exome

AF:

0.00490

Gnomad4 ASJ exome

AF:

0.0344

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00471

Gnomad4 FIN exome

AF:

0.0283

Gnomad4 NFE exome

AF:

0.00364

Gnomad4 OTH exome

AF:

0.0109

GnomAD4 genome

AF:

0.0194

AC:

2949

AN:

152242

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1502

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0483

Gnomad4 AMR

AF:

0.00961

Gnomad4 ASJ

AF:

0.0325

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0300

Gnomad4 NFE

AF:

0.00451

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0144

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely 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. -

not specified

Benign:1

Likely 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

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.5

DANN

Benign

0.60

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