Variant 21-44305863-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001002021.3(PFKL):c.163C>T(p.Arg55*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0429 in 1,366,024 control chromosomes in the GnomAD database, including 1,515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.032 ( 140 hom., cov: 33)

Exomes 𝑓: 0.044 ( 1375 hom. )

Consequence

PFKL
NM_001002021.3 stop_gained

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.286

Variant links:

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]

PFKL links:

PFKL (HGNC:):

PFKL links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 21-44305863-C-T is Benign according to our data. Variant chr21-44305863-C-T is described in ClinVar as [Benign]. Clinvar id is 3059937.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0323 (4917/152216) while in subpopulation NFE AF= 0.0485 (3294/67980). AF 95% confidence interval is 0.0471. There are 140 homozygotes in gnomad4. There are 2237 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 140 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKL	NM_002626.6 linkuse as main transcript	c.86-818C>T		intron_variant		ENST00000349048.9	NP_002617.3	P17858-1Q7L2M7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKL	ENST00000349048.9 linkuse as main transcript	c.86-818C>T		intron_variant		1	NM_002626.6	ENSP00000269848.6		P17858-1

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4918

AN:

152098

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00954

Gnomad AMI

AF:

0.0691

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0172

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0484

Gnomad OTH

AF:

0.0415

GnomAD3 exomes

AF:

0.0319

AC:

7890

AN:

247646

Hom.:

172

AF XY:

0.0326

AC XY:

4374

AN XY:

134298

show subpopulations

Gnomad AFR exome

AF:

0.00869

Gnomad AMR exome

AF:

0.0252

Gnomad ASJ exome

AF:

0.0479

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0174

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0474

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0442

AC:

53685

AN:

1213808

Hom.:

1375

Cov.:

AF XY:

0.0436

AC XY:

26199

AN XY:

601366

show subpopulations

Gnomad4 AFR exome

AF:

0.00689

Gnomad4 AMR exome

AF:

0.0268

Gnomad4 ASJ exome

AF:

0.0491

Gnomad4 EAS exome

AF:

0.000119

Gnomad4 SAS exome

AF:

0.0183

Gnomad4 FIN exome

AF:

0.0189

Gnomad4 NFE exome

AF:

0.0500

Gnomad4 OTH exome

AF:

0.0389

GnomAD4 genome

AF:

0.0323

AC:

4917

AN:

152216

Hom.:

140

Cov.:

AF XY:

0.0301

AC XY:

2237

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.00951

Gnomad4 AMR

AF:

0.0403

Gnomad4 ASJ

AF:

0.0487

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0172

Gnomad4 NFE

AF:

0.0485

Gnomad4 OTH

AF:

0.0406

Alfa

AF:

0.0425

Hom.:

100

Bravo

AF:

0.0341

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PFKL-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 05, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.4

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

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