12-48106148-A-T

Position:

• chr12-48106148-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001354735.1(PFKM):​c.-114A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 702,158 control chromosomes in the GnomAD database, including 7,409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1392 hom., cov: 32)
  • Exomes 𝑓: 0.14 (6017 hom.)
• Consequence: PFKM NM_001354735.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.318

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-48106148-A-T is Benign according to our data. Variant chr12-48106148-A-T is described in ClinVar as [Benign]. Clinvar id is 1239017.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKM	NM_001354735.1	c.-114A>T		5_prime_UTR_variant	1/26
PFKM	NM_001354736.1	c.-173A>T		5_prime_UTR_variant	1/26
PFKM	NM_001354737.1	c.-173A>T		5_prime_UTR_variant	1/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKM	ENST00000546755.5	c.-173A>T		5_prime_UTR_variant	1/5	4
PFKM	ENST00000549366.5	c.-43A>T		5_prime_UTR_variant	1/7	4
PFKM	ENST00000552792.5	c.-173A>T		5_prime_UTR_variant	1/6	4

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17879 AN: 152150 Hom.: 1391 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.142

GnomAD3 exomes AF: 0.131 AC: 16903 AN: 129454 Hom.: 1399 AF XY: 0.128 AC XY: 9037 AN XY: 70788

Gnomad AFR exome AF: 0.0290

Gnomad AMR exome AF: 0.0953

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.248

Gnomad SAS exome AF: 0.0528

Gnomad FIN exome AF: 0.0985

Gnomad NFE exome AF: 0.158

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.139 AC: 76327 AN: 549890 Hom.: 6017 Cov.: 0 AF XY: 0.135 AC XY: 40156 AN XY: 297686

Gnomad4 AFR exome AF: 0.0330

Gnomad4 AMR exome AF: 0.0980

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.0553

Gnomad4 FIN exome AF: 0.0932

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.117 AC: 17873 AN: 152268 Hom.: 1392 Cov.: 32 AF XY: 0.114 AC XY: 8468 AN XY: 74462

Gnomad4 AFR AF: 0.0320

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.235

Gnomad4 SAS AF: 0.0620

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.141

Alfa AF: 0.145 Hom.: 333

Bravo AF: 0.119

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4760619; hg19: chr12-48499931;