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12-48106115-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The ENST00000550257.7(PFKM):c.69C>T(p.Phe23=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 702,678 control chromosomes in the GnomAD database, including 212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.018 ( 37 hom., cov: 32)
Exomes 𝑓: 0.021 ( 175 hom. )

Consequence

PFKM
ENST00000550257.7 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0460
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-48106115-C-T is Benign according to our data. Variant chr12-48106115-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1211158.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.046 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0184 (2810/152342) while in subpopulation NFE AF= 0.0269 (1828/68030). AF 95% confidence interval is 0.0258. There are 37 homozygotes in gnomad4. There are 1374 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 37 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SENP1NM_001267594.2 linkuse as main transcript upstream_gene_variant ENST00000549518.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SENP1ENST00000549518.6 linkuse as main transcript upstream_gene_variant 1 NM_001267594.2 P4Q9P0U3-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0185
AC:
2811
AN:
152224
Hom.:
37
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00456
Gnomad AMI
AF:
0.0537
Gnomad AMR
AF:
0.0212
Gnomad ASJ
AF:
0.0138
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00435
Gnomad FIN
AF:
0.0283
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.0269
Gnomad OTH
AF:
0.0210
GnomAD3 exomes
AF:
0.0159
AC:
2086
AN:
130898
Hom.:
25
AF XY:
0.0155
AC XY:
1112
AN XY:
71570
show subpopulations
Gnomad AFR exome
AF:
0.00353
Gnomad AMR exome
AF:
0.0137
Gnomad ASJ exome
AF:
0.0140
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00509
Gnomad FIN exome
AF:
0.0269
Gnomad NFE exome
AF:
0.0254
Gnomad OTH exome
AF:
0.0223
GnomAD4 exome
AF:
0.0208
AC:
11472
AN:
550336
Hom.:
175
Cov.:
0
AF XY:
0.0205
AC XY:
6112
AN XY:
297944
show subpopulations
Gnomad4 AFR exome
AF:
0.00361
Gnomad4 AMR exome
AF:
0.0147
Gnomad4 ASJ exome
AF:
0.0147
Gnomad4 EAS exome
AF:
0.0000311
Gnomad4 SAS exome
AF:
0.00534
Gnomad4 FIN exome
AF:
0.0252
Gnomad4 NFE exome
AF:
0.0278
Gnomad4 OTH exome
AF:
0.0184
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0184
AC:
2810
AN:
152342
Hom.:
37
Cov.:
32
AF XY:
0.0184
AC XY:
1374
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.00455
Gnomad4 AMR
AF:
0.0212
Gnomad4 ASJ
AF:
0.0138
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00435
Gnomad4 FIN
AF:
0.0283
Gnomad4 NFE
AF:
0.0269
Gnomad4 OTH
AF:
0.0208
Alfa
AF:
0.0235
Hom.:
7
Bravo
AF:
0.0171
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
14
Dann
Benign
0.95

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.

Other links and lift over

dbSNP: rs140895856; hg19: chr12-48499898; API