rs2243523

Variant names:

• chr17-82722573-G-T
• rs2243523
• NM_024619.4:c.386-231G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 30 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024619.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3KRP	NM_024619.4	MANE Select	c.386-231G>T		intron	N/A	NP_078895.2
	FN3KRP	NR_046408.2		n.564-231G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3KRP	ENST00000269373.11	TSL:1 MANE Select	c.386-231G>T		intron	N/A	ENSP00000269373.6
	FN3KRP	ENST00000577128.1	TSL:5	c.236-231G>T		intron	N/A	ENSP00000459653.1
	FN3KRP	ENST00000573158.5	TSL:3	c.-143-231G>T		intron	N/A	ENSP00000460243.1

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

African (AFR) AF: 0.392 AC: 4016 AN: 10238

American (AMR) AF: 0.438 AC: 4927 AN: 11260

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 3275 AN: 11064

East Asian (EAS) AF: 0.438 AC: 10515 AN: 24018

South Asian (SAS) AF: 0.246 AC: 8814 AN: 35856

European-Finnish (FIN) AF: 0.455 AC: 9638 AN: 21202

Middle Eastern (MID) AF: 0.300 AC: 470 AN: 1566

European-Non Finnish (NFE) AF: 0.379 AC: 80764 AN: 213138

Other (OTH) AF: 0.373 AC: 7586 AN: 20346

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

African (AFR) AF: 0.399 AC: 16561 AN: 41502

American (AMR) AF: 0.421 AC: 6432 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1080 AN: 3472

East Asian (EAS) AF: 0.412 AC: 2128 AN: 5164

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4822

European-Finnish (FIN) AF: 0.459 AC: 4851 AN: 10572

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26394 AN: 67952

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.378 Hom.: 35959

Bravo AF: 0.394

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.72
PhyloP100		-0.93
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: rs2243523; hg19: chr17-80680449;