rs726354

Variant names:

• chr12-48106551-G-A
• rs726354
• ENST00000942229.1:c.-1306G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-48106551-G-A
• chr12-48106551-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001354735.1(PFKM):​c.-10+299G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 209,332 control chromosomes in the GnomAD database, including 6,405 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (4671 hom., cov: 31)
  • Exomes 𝑓: 0.22 (1734 hom.)
• Consequence: PFKM NM_001354735.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 6 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]

SENP1 (HGNC:17927): (SUMO specific peptidase 1) This gene encodes a cysteine protease that specifically targets members of the small ubiquitin-like modifier (SUMO) protein family. This protease regulates SUMO pathways by deconjugating sumoylated proteins. This protease also functions to process the precursor SUMO proteins into their mature form. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354735.1. 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_001354735.1		c.-10+299G>A		intron	N/A	NP_001341664.1	A0A2R8Y891
	PFKM	NM_001354736.1		c.-10+240G>A		intron	N/A	NP_001341665.1	A0A2R8Y891
	PFKM	NM_001166686.2		c.-10+414G>A		intron	N/A	NP_001160158.1	P08237-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	ENST00000942229.1		c.-1306G>A		5_prime_UTR	Exon 1 of 25	ENSP00000612288.1
	PFKM	ENST00000642730.1		c.-10+299G>A		intron	N/A	ENSP00000496597.1	A0A2R8Y891
	PFKM	ENST00000550257.7	TSL:4	c.91+414G>A		intron	N/A	ENSP00000447997.3	F8VTQ3

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34493 AN: 151838 Hom.: 4660 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.224 AC: 12873 AN: 57374 Hom.: 1734 Cov.: 0 AF XY: 0.236 AC XY: 7200 AN XY: 30534

African (AFR) AF: 0.197 AC: 137 AN: 694

American (AMR) AF: 0.427 AC: 1511 AN: 3540

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 301 AN: 1470

East Asian (EAS) AF: 0.586 AC: 714 AN: 1218

South Asian (SAS) AF: 0.320 AC: 3436 AN: 10732

European-Finnish (FIN) AF: 0.230 AC: 649 AN: 2824

Middle Eastern (MID) AF: 0.174 AC: 32 AN: 184

European-Non Finnish (NFE) AF: 0.162 AC: 5449 AN: 33654

Other (OTH) AF: 0.211 AC: 644 AN: 3058

GnomAD4 genome AF: 0.227 AC: 34532 AN: 151958 Hom.: 4671 Cov.: 31 AF XY: 0.237 AC XY: 17582 AN XY: 74276

African (AFR) AF: 0.223 AC: 9254 AN: 41424

American (AMR) AF: 0.364 AC: 5555 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3464

East Asian (EAS) AF: 0.590 AC: 3042 AN: 5156

South Asian (SAS) AF: 0.353 AC: 1695 AN: 4806

European-Finnish (FIN) AF: 0.234 AC: 2472 AN: 10570

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11071 AN: 67954

Other (OTH) AF: 0.229 AC: 482 AN: 2106

Alfa AF: 0.199 Hom.: 519

Bravo AF: 0.239

Asia WGS AF: 0.454 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.77
PhyloP100		0.25
PromoterAI		-0.016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs726354; hg19: chr12-48500334;