chr12-48141297-G-T

Variant names:

• chr12-48141297-G-T
• rs56117548
• NM_000289.6:c.1342-14G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000289.6(PFKM):​c.1342-14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,612,984 control chromosomes in the GnomAD database, including 803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (51 hom., cov: 32)
  • Exomes 𝑓: 0.029 (752 hom.)
• Consequence: PFKM NM_000289.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.410
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• glycogen storage disease VII

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-48141297-G-T is Benign according to our data. Variant chr12-48141297-G-T is described in ClinVar as Benign. ClinVar VariationId is 255750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000289.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	NM_000289.6	MANE Select	c.1342-14G>T		intron	N/A	NP_000280.1	P08237-1
	PFKM	NM_001354735.1		c.1651-14G>T		intron	N/A	NP_001341664.1	A0A2R8Y891
	PFKM	NM_001354736.1		c.1651-14G>T		intron	N/A	NP_001341665.1	A0A2R8Y891

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	ENST00000359794.11	TSL:1 MANE Select	c.1342-14G>T		intron	N/A	ENSP00000352842.5	P08237-1
	PFKM	ENST00000312352.11	TSL:1	c.1342-14G>T		intron	N/A	ENSP00000309438.7	P08237-1
	PFKM	ENST00000547587.5	TSL:1	c.1342-14G>T		intron	N/A	ENSP00000449426.1	P08237-1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3215 AN: 152156 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00574

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0149

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.0570

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0272

GnomAD2 exomes AF: 0.0253 AC: 6357 AN: 251428 AF XY: 0.0282

Gnomad AFR exome AF: 0.00486

Gnomad AMR exome AF: 0.00986

Gnomad ASJ exome AF: 0.0106

Gnomad EAS exome AF: 0.00652

Gnomad FIN exome AF: 0.0265

Gnomad NFE exome AF: 0.0287

Gnomad OTH exome AF: 0.0199

GnomAD4 exome AF: 0.0288 AC: 42094 AN: 1460710 Hom.: 752 Cov.: 31 AF XY: 0.0298 AC XY: 21691 AN XY: 726742

African (AFR) AF: 0.00490 AC: 164 AN: 33470

American (AMR) AF: 0.0105 AC: 470 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00976 AC: 255 AN: 26136

East Asian (EAS) AF: 0.00597 AC: 237 AN: 39696

South Asian (SAS) AF: 0.0559 AC: 4824 AN: 86220

European-Finnish (FIN) AF: 0.0274 AC: 1462 AN: 53420

Middle Eastern (MID) AF: 0.00834 AC: 48 AN: 5756

European-Non Finnish (NFE) AF: 0.0299 AC: 33185 AN: 1110924

Other (OTH) AF: 0.0240 AC: 1449 AN: 60366

GnomAD4 genome AF: 0.0211 AC: 3213 AN: 152274 Hom.: 51 Cov.: 32 AF XY: 0.0213 AC XY: 1588 AN XY: 74456

African (AFR) AF: 0.00570 AC: 237 AN: 41552

American (AMR) AF: 0.0148 AC: 227 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3468

East Asian (EAS) AF: 0.00792 AC: 41 AN: 5174

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4820

European-Finnish (FIN) AF: 0.0256 AC: 272 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2021 AN: 68012

Other (OTH) AF: 0.0279 AC: 59 AN: 2116

Alfa AF: 0.0222 Hom.: 8

Bravo AF: 0.0185

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Glycogen storage disease, type VII (4)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.6
DANN	Benign	0.62
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs56117548; hg19: chr12-48535080; COSMIC: COSV107349446; COSMIC: COSV107349446;