21-44312233-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_002626.6(PFKL):c.366C>T(p.Leu122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 1,596,274 control chromosomes in the GnomAD database, including 254,071 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (19379 hom., cov: 34)
  • Exomes 𝑓: 0.57 (234692 hom.)
• Consequence: PFKL NM_002626.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.384

Genes affected

PFKL (HGNC:8876): (phosphofructokinase, liver type) This gene encodes the liver (L) subunit of an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 21-44312233-C-T is Benign according to our data. Variant chr21-44312233-C-T is described in ClinVar as [Benign]. Clinvar id is 440032.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.384 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKL	NM_002626.6	c.366C>T	p.Leu122=	synonymous_variant	4/22	ENST00000349048.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKL	ENST00000349048.9	c.366C>T	p.Leu122=	synonymous_variant	4/22	1	NM_002626.6	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74365 AN: 152030 Hom.: 19377 Cov.: 34

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.516

GnomAD3 exomes AF: 0.525 AC: 116579 AN: 222264 Hom.: 31341 AF XY: 0.534 AC XY: 64925 AN XY: 121490

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.488

Gnomad ASJ exome AF: 0.511

Gnomad EAS exome AF: 0.354

Gnomad SAS exome AF: 0.581

Gnomad FIN exome AF: 0.512

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.542

GnomAD4 exome AF: 0.566 AC: 817893 AN: 1444128 Hom.: 234692 Cov.: 50 AF XY: 0.568 AC XY: 407614 AN XY: 717358

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.516

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.579

Gnomad4 FIN exome AF: 0.521

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.489 AC: 74378 AN: 152146 Hom.: 19379 Cov.: 34 AF XY: 0.484 AC XY: 35984 AN XY: 74372

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.514

Alfa AF: 0.563 Hom.: 28354

Bravo AF: 0.479

Asia WGS AF: 0.497 AC: 1723 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jan 09, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	5.7
Dann	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1057034; hg19: chr21-45732116; COSMIC: COSV62463352; COSMIC: COSV62463352;