rs2243523

Positions:

• chr17-82722573-G-T

Variant summary

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

The NM_024619.4(FN3KRP):​c.386-231G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 500,764 control chromosomes in the GnomAD database, including 37,063 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 0.39 (11962 hom., cov: 33)
  • Exomes 𝑓: 0.37 (25101 hom.)
• Consequence: FN3KRP NM_024619.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.930

Genes affected

FN3KRP (HGNC:25700): (fructosamine 3 kinase related protein) A high concentration of glucose can result in non-enzymatic oxidation of proteins by reaction of glucose and lysine residues (glycation). Proteins modified in this way are less active or functional. This gene encodes an enzyme which catalyzes the phosphorylation of psicosamines and ribulosamines compared to the neighboring gene which encodes a highly similar enzyme, fructosamine-3-kinase, which has different substrate specificity. The activity of both enzymes may result in deglycation of proteins to restore their function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

FN3KRP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FN3KRP	NM_024619.4	c.386-231G>T		intron_variant		ENST00000269373.11	NP_078895.2
FN3KRP	NR_046408.2	n.564-231G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FN3KRP	ENST00000269373.11	c.386-231G>T		intron_variant		1	NM_024619.4	ENSP00000269373.6

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59777 AN: 151958 Hom.: 11967 Cov.: 33

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.373 AC: 130005 AN: 348688 Hom.: 25101 Cov.: 3 AF XY: 0.364 AC XY: 66664 AN XY: 183176

Gnomad4 AFR exome AF: 0.392

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.246

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.373

GnomAD4 genome AF: 0.393 AC: 59807 AN: 152076 Hom.: 11962 Cov.: 33 AF XY: 0.393 AC XY: 29209 AN XY: 74332

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.459

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.342

Alfa AF: 0.374 Hom.: 21903

Bravo AF: 0.394

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.72

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: rs2243523; hg19: chr17-80680449;