rs2228501

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The ENST00000359794.11(PFKM):c.246G>A(p.Thr82Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 1,611,564 control chromosomes in the GnomAD database, including 6,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 361 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5663 hom. )

Consequence

PFKM
ENST00000359794.11 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.04

Publications

8 publications found

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:

MIR6505 (HGNC:50104): (microRNA 6505) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6505 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 12-48132876-G-A is Benign according to our data. Variant chr12-48132876-G-A is described in ClinVar as Benign. ClinVar VariationId is 255759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359794.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PFKM	NM_000289.6	MANE Select	c.246G>A	p.Thr82Thr	synonymous	Exon 5 of 23	NP_000280.1
PFKM	NM_001354735.1		c.555G>A	p.Thr185Thr	synonymous	Exon 8 of 26	NP_001341664.1
PFKM	NM_001354736.1		c.555G>A	p.Thr185Thr	synonymous	Exon 8 of 26	NP_001341665.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PFKM	ENST00000359794.11	TSL:1 MANE Select	c.246G>A	p.Thr82Thr	synonymous	Exon 5 of 23	ENSP00000352842.5
PFKM	ENST00000312352.11	TSL:1	c.246G>A	p.Thr82Thr	synonymous	Exon 5 of 23	ENSP00000309438.7
PFKM	ENST00000547587.5	TSL:1	c.246G>A	p.Thr82Thr	synonymous	Exon 4 of 22	ENSP00000449426.1

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

9099

AN:

152116

Hom.:

361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0244

Gnomad AMI

AF:

0.0164

Gnomad AMR

AF:

0.0408

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.0839

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.0929

Gnomad OTH

AF:

0.0540

GnomAD2 exomes

AF:

0.0571

AC:

14072

AN:

246558

AF XY:

0.0572

show subpopulations

Gnomad AFR exome

AF:

0.0202

Gnomad AMR exome

AF:

0.0289

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.000386

Gnomad FIN exome

AF:

0.0827

Gnomad NFE exome

AF:

0.0904

Gnomad OTH exome

AF:

0.0581

GnomAD4 exome

AF:

0.0816

AC:

119092

AN:

1459330

Hom.:

5663

Cov.:

AF XY:

0.0795

AC XY:

57689

AN XY:

725796

show subpopulations

African (AFR)

AF:

0.0201

AC:

671

AN:

33454

American (AMR)

AF:

0.0301

AC:

1339

AN:

44436

Ashkenazi Jewish (ASJ)

AF:

0.0168

AC:

439

AN:

26062

East Asian (EAS)

AF:

0.000504

AC:

AN:

39654

South Asian (SAS)

AF:

0.0161

AC:

1384

AN:

85884

European-Finnish (FIN)

AF:

0.0836

AC:

4458

AN:

53310

Middle Eastern (MID)

AF:

0.0151

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0959

AC:

106545

AN:

1110448

Other (OTH)

AF:

0.0688

AC:

4149

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

5435

10870

16305

21740

27175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3790

7580

11370

15160

18950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0598

AC:

9101

AN:

152234

Hom.:

361

Cov.:

AF XY:

0.0582

AC XY:

4329

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0244

AC:

1013

AN:

41560

American (AMR)

AF:

0.0408

AC:

624

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0159

AC:

AN:

3470

East Asian (EAS)

AF:

0.000966

AC:

AN:

5174

South Asian (SAS)

AF:

0.0139

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0839

AC:

888

AN:

10586

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0929

AC:

6317

AN:

67990

Other (OTH)

AF:

0.0534

AC:

113

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

440

880

1319

1759

2199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0722

Hom.:

317

Bravo

AF:

0.0532

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease, type VII (4)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.0

(source)

DANN

Benign

0.74

PhyloP100

-2.0

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.24

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over