rs2838549

Positions:

• chr21-44315002-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002626.6(PFKL):​c.747+981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,318 control chromosomes in the GnomAD database, including 578 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.084 (578 hom., cov: 34)
  • Exomes 𝑓: 0.038 (0 hom.)
• Consequence: PFKL NM_002626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.30

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PFKL	NM_002626.6	c.747+981G>A		intron_variant		ENST00000349048.9	NP_002617.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFKL	ENST00000349048.9	c.747+981G>A		intron_variant		1	NM_002626.6	ENSP00000269848.6
PFKL	ENST00000397961.6	n.*1096+981G>A		intron_variant		1		ENSP00000381052.2
PFKL	ENST00000466134.5	n.1738G>A		non_coding_transcript_exon_variant	7/20	2
PFKL	ENST00000496824.5	n.967+981G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12850 AN: 152148 Hom.: 576 Cov.: 34

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0954

Gnomad EAS AF: 0.00634

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.0706

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0782

Gnomad OTH AF: 0.0913

GnomAD4 exome AF: 0.0385 AC: 2 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 32

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0845 AC: 12860 AN: 152266 Hom.: 578 Cov.: 34 AF XY: 0.0839 AC XY: 6244 AN XY: 74450

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0666

Gnomad4 ASJ AF: 0.0954

Gnomad4 EAS AF: 0.00636

Gnomad4 SAS AF: 0.0979

Gnomad4 FIN AF: 0.0706

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0799 Hom.: 413

Bravo AF: 0.0850

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs2838549; hg19: chr21-45734885;