rs11168427

Variant names:

• chr12-48145196-A-G
• rs11168427
• NM_000289.6:c.2093-14A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-48145196-A-G
• chr12-48145196-A-C

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.2093-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,613,036 control chromosomes in the GnomAD database, including 34,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2441 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31623 hom.)
• Consequence: PFKM NM_000289.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.564
• Publications: 14 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=-0.85).
• BP6: Variant 12-48145196-A-G is Benign according to our data. Variant chr12-48145196-A-G is described in ClinVar as Benign. ClinVar VariationId is 255757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 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.2093-14A>G		intron	N/A	NP_000280.1	P08237-1
	PFKM	NM_001354735.1		c.2402-14A>G		intron	N/A	NP_001341664.1	A0A2R8Y891
	PFKM	NM_001354736.1		c.2402-14A>G		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.2093-14A>G		intron	N/A	ENSP00000352842.5	P08237-1
	PFKM	ENST00000312352.11	TSL:1	c.2093-14A>G		intron	N/A	ENSP00000309438.7	P08237-1
	PFKM	ENST00000547587.5	TSL:1	c.2093-14A>G		intron	N/A	ENSP00000449426.1	P08237-1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25283 AN: 152008 Hom.: 2439 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.204

GnomAD2 exomes AF: 0.178 AC: 44862 AN: 251360 AF XY: 0.182

Gnomad AFR exome AF: 0.0690

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.253

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.210

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.204 AC: 298028 AN: 1460910 Hom.: 31623 Cov.: 32 AF XY: 0.203 AC XY: 147277 AN XY: 726816

African (AFR) AF: 0.0689 AC: 2307 AN: 33464

American (AMR) AF: 0.123 AC: 5485 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 7017 AN: 26134

East Asian (EAS) AF: 0.227 AC: 8999 AN: 39696

South Asian (SAS) AF: 0.139 AC: 11995 AN: 86234

European-Finnish (FIN) AF: 0.135 AC: 7225 AN: 53420

Middle Eastern (MID) AF: 0.206 AC: 1189 AN: 5768

European-Non Finnish (NFE) AF: 0.217 AC: 241552 AN: 1111110

Other (OTH) AF: 0.203 AC: 12259 AN: 60360

GnomAD4 genome AF: 0.166 AC: 25285 AN: 152126 Hom.: 2441 Cov.: 32 AF XY: 0.163 AC XY: 12124 AN XY: 74360

African (AFR) AF: 0.0725 AC: 3011 AN: 41528

American (AMR) AF: 0.181 AC: 2768 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3472

East Asian (EAS) AF: 0.242 AC: 1246 AN: 5152

South Asian (SAS) AF: 0.148 AC: 715 AN: 4824

European-Finnish (FIN) AF: 0.129 AC: 1360 AN: 10578

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14629 AN: 67970

Other (OTH) AF: 0.203 AC: 428 AN: 2112

Alfa AF: 0.203 Hom.: 5607

Bravo AF: 0.166

Asia WGS AF: 0.155 AC: 538 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	-0.85
CADD	Benign	0.10
DANN	Benign	0.36
PhyloP100		-0.56
Mutation Taster		=12/88	disease causing

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

Other links and lift over

dbSNP: rs11168427; hg19: chr12-48538979; COSMIC: COSV56656555; COSMIC: COSV56656555;