ENST00000550257.7:c.69C>T

Variant names:

• chr12-48106115-C-T
• rs140895856
• ENST00000550257.7:c.69C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000550257.7(PFKM):​c.69C>T​(p.Phe23Phe) 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0460
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 12-48106115-C-T is Benign according to our data. Variant chr12-48106115-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1211158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.046 with no splicing effect.
• BS1: 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000550257.7. 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_001166686.2		c.-32C>T		5_prime_UTR	Exon 1 of 25	NP_001160158.1	P08237-3
	PFKM	NM_001439058.1		c.-206C>T		5_prime_UTR	Exon 1 of 24	NP_001425987.1
	PFKM	NM_001354741.2		c.-81+696C>T		intron	N/A	NP_001341670.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PFKM	ENST00000550257.7	TSL:4	c.69C>T	p.Phe23Phe	synonymous	Exon 1 of 24	ENSP00000447997.3	F8VTQ3
	PFKM	ENST00000340802.12	TSL:2	c.-32C>T		5_prime_UTR	Exon 1 of 25	ENSP00000345771.6	P08237-3
	PFKM	ENST00000873520.1		c.-31C>T		5_prime_UTR	Exon 1 of 23	ENSP00000543579.1

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2811 AN: 152224 Hom.: 37 Cov.: 32

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

GnomAD2 exomes AF: 0.0159 AC: 2086 AN: 130898 AF XY: 0.0155

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 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

African (AFR) AF: 0.00361 AC: 57 AN: 15800

American (AMR) AF: 0.0147 AC: 510 AN: 34706

Ashkenazi Jewish (ASJ) AF: 0.0147 AC: 295 AN: 20024

East Asian (EAS) AF: 0.0000311 AC: 1 AN: 32104

South Asian (SAS) AF: 0.00534 AC: 335 AN: 62758

European-Finnish (FIN) AF: 0.0252 AC: 844 AN: 33540

Middle Eastern (MID) AF: 0.0118 AC: 48 AN: 4062

European-Non Finnish (NFE) AF: 0.0278 AC: 8819 AN: 316756

Other (OTH) AF: 0.0184 AC: 563 AN: 30586

GnomAD4 genome AF: 0.0184 AC: 2810 AN: 152342 Hom.: 37 Cov.: 32 AF XY: 0.0184 AC XY: 1374 AN XY: 74498

African (AFR) AF: 0.00455 AC: 189 AN: 41580

American (AMR) AF: 0.0212 AC: 324 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4826

European-Finnish (FIN) AF: 0.0283 AC: 301 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0269 AC: 1828 AN: 68030

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.0235 Hom.: 7

Bravo AF: 0.0171

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		0.046
PromoterAI		0.021	Neutral
Mutation Taster		=299/1	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs140895856; hg19: chr12-48499898;