rs3788116

Variant names:

• chr21-44302559-C-T
• rs3788116
• NM_002626.6:c.85+2369C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PFKL	NM_002626.6	c.85+2369C>T		intron_variant	Intron 1 of 21	ENST00000349048.9	NP_002617.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PFKL	ENST00000349048.9	c.85+2369C>T		intron_variant	Intron 1 of 21	1	NM_002626.6	ENSP00000269848.6

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

African (AFR) AF: 0.523 AC: 21706 AN: 41496

American (AMR) AF: 0.337 AC: 5156 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1253 AN: 5184

South Asian (SAS) AF: 0.262 AC: 1265 AN: 4822

European-Finnish (FIN) AF: 0.300 AC: 3171 AN: 10572

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17310 AN: 67982

Other (OTH) AF: 0.329 AC: 692 AN: 2106

Alfa AF: 0.283 Hom.: 5105

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3788116; hg19: chr21-45722442;