21-44300101-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.879

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 -12 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_single_submitter, 1 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 GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKL	NM_002626.6	c.-5C>T		5_prime_UTR_variant	1/22	ENST00000349048.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKL	ENST00000349048.9	c.-5C>T		5_prime_UTR_variant	1/22	1	NM_002626.6	P1

Frequencies

GnomAD3 genomes AF: 0.00573 AC: 848 AN: 148048 Hom.: 11 Cov.: 33

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: 34 AN: 53938 Hom.: 1 AF XY: 0.000435 AC XY: 14 AN XY: 32178

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.: 7 Cov.: 29 AF XY: 0.000591 AC XY: 288 AN XY: 487514

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.: 11 Cov.: 33 AF XY: 0.00580 AC XY: 419 AN XY: 72194

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.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 04, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	15
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

Other links and lift over

dbSNP: rs550375523; hg19: chr21-45719984;