Genetic Variant PFKM:c.-114A>T (chr12-48106148-A-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.318

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:

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]

SENP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SENP1	NM_001267594.2 link	c.-165T>A		upstream_gene_variant		ENST00000549518.6	NP_001254523.1	Q9P0U3-1Q6N001

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SENP1	ENST00000549518.6 link	c.-165T>A		upstream_gene_variant		1	NM_001267594.2	ENSP00000447328.1		Q9P0U3-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17879

AN:

152150

Hom.:

1391

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.135

AC XY:

40156

AN XY:

297686

show subpopulations

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.:

AF XY:

0.114

AC XY:

8468

AN XY:

74462

show subpopulations

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over