chr12-48108360-G-A

Position:

• chr12-48108360-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001354735.1(PFKM):​c.205+166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 152,064 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.023 (61 hom., cov: 32)
• Consequence: PFKM NM_001354735.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.473

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 12-48108360-G-A is Benign according to our data. Variant chr12-48108360-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1201899.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0232 (3531/152064) while in subpopulation NFE AF= 0.0349 (2374/67996). AF 95% confidence interval is 0.0337. There are 61 homozygotes in gnomad4. There are 1703 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKM	NM_001354735.1	c.205+166G>A		intron_variant			NP_001341664.1
PFKM	NM_001354736.1	c.205+166G>A		intron_variant			NP_001341665.1
PFKM	NM_001166686.2	c.205+166G>A		intron_variant			NP_001160158.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKM	ENST00000642730.1	c.205+166G>A		intron_variant				ENSP00000496597.1
PFKM	ENST00000550257.7	c.214+166G>A		intron_variant		4		ENSP00000447997.3
PFKM	ENST00000340802.12	c.205+166G>A		intron_variant		2		ENSP00000345771.6

Frequencies

GnomAD3 genomes AF: 0.0232 AC: 3530 AN: 151946 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.00613

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0311

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0349

Gnomad OTH AF: 0.0225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0232 AC: 3531 AN: 152064 Hom.: 61 Cov.: 32 AF XY: 0.0229 AC XY: 1703 AN XY: 74354

Gnomad4 AFR AF: 0.00613

Gnomad4 AMR AF: 0.0165

Gnomad4 ASJ AF: 0.0311

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.0349

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0282 Hom.: 10

Bravo AF: 0.0222

Asia WGS AF: 0.00462 AC: 17 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 07, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs73102080; hg19: chr12-48502143;