Variant 21-44300101-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_002626.6(PFKL):c.-5C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,148,538 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 11 hom., cov: 33)

Exomes 𝑓: 0.00071 ( 7 hom. )

Consequence

PFKL
NM_002626.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.879

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 21-44300101-C-T is Benign according to our data. Variant chr21-44300101-C-T is described in ClinVar as [Benign]. Clinvar id is 618268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00576 (854/148156) while in subpopulation AFR AF= 0.0195 (801/41126). AF 95% confidence interval is 0.0184. There are 11 homozygotes in gnomad4. There are 419 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKL	NM_002626.6 linkuse as main transcript	c.-5C>T		5_prime_UTR_variant	1/22	ENST00000349048.9	NP_002617.3	P17858-1Q7L2M7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKL	ENST00000349048 linkuse as main transcript	c.-5C>T		5_prime_UTR_variant	1/22	1	NM_002626.6	ENSP00000269848.6		P17858-1

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

848

AN:

148048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00168

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.000211

Gnomad OTH

AF:

0.00440

GnomAD3 exomes

AF:

0.000630

AC:

AN:

53938

Hom.:

AF XY:

0.000435

AC XY:

AN XY:

32178

show subpopulations

Gnomad AFR exome

AF:

0.0192

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000305

Gnomad OTH exome

AF:

0.00187

GnomAD4 exome

AF:

0.000707

AC:

707

AN:

1000382

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

288

AN XY:

487514

show subpopulations

Gnomad4 AFR exome

AF:

0.0236

Gnomad4 AMR exome

AF:

0.00177

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00576

AC:

854

AN:

148156

Hom.:

Cov.:

AF XY:

0.00580

AC XY:

419

AN XY:

72194

show subpopulations

Gnomad4 AFR

AF:

0.0195

Gnomad4 AMR

AF:

0.00168

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000211

Gnomad4 OTH

AF:

0.00436

Alfa

AF:

0.00434

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 04, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.2

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