rs3788116

chr21-44302559-C-T

Variant summary

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

The NM_002626.6(PFKL):c.85+2369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,112 control chromosomes in the GnomAD database, including 10,042 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 0.34 (10042 hom., cov: 33)
• Consequence: PFKL NM_002626.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PFKL	NM_002626.6	c.85+2369C>T		intron_variant		ENST00000349048.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PFKL	ENST00000349048.9	c.85+2369C>T		intron_variant		1	NM_002626.6	P1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52087 AN: 151994 Hom.: 10015 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.343 AC: 52153 AN: 152112 Hom.: 10042 Cov.: 33 AF XY: 0.344 AC XY: 25560 AN XY: 74366

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.255

Gnomad4 OTH AF: 0.329

Alfa AF: 0.279 Hom.: 4106

Bravo AF: 0.354

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.4
Dann	Benign	0.35

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: rs3788116; hg19: chr21-45722442;