rs1046889

Variant names:

• chr17-82727635-C-T
• rs1046889
• NM_024619.4:c.*464C>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.*464C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 157,134 control chromosomes in the GnomAD database, including 3,416 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 0.19 (3368 hom., cov: 34)
  • Exomes 𝑓: 0.13 (48 hom.)
• Consequence: FN3KRP NM_024619.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 23 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 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.*464C>T		3_prime_UTR	Exon 6 of 6	NP_078895.2
	FN3KRP	NR_046408.2		n.1572C>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3KRP	ENST00000269373.11	TSL:1 MANE Select	c.*464C>T		3_prime_UTR	Exon 6 of 6	ENSP00000269373.6
	FN3KRP	ENST00000571594.1	TSL:3	n.53+468C>T		intron	N/A	ENSP00000459751.1
	FN3KRP	ENST00000574832.5	TSL:2	n.*1351C>T		downstream_gene	N/A	ENSP00000460869.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28429 AN: 152116 Hom.: 3354 Cov.: 34

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.127 AC: 621 AN: 4900 Hom.: 48 Cov.: 0 AF XY: 0.127 AC XY: 322 AN XY: 2536

African (AFR) AF: 0.309 AC: 34 AN: 110

American (AMR) AF: 0.0647 AC: 36 AN: 556

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 15 AN: 94

East Asian (EAS) AF: 0.0676 AC: 15 AN: 222

South Asian (SAS) AF: 0.228 AC: 41 AN: 180

European-Finnish (FIN) AF: 0.136 AC: 29 AN: 214

Middle Eastern (MID) AF: 0.278 AC: 5 AN: 18

European-Non Finnish (NFE) AF: 0.125 AC: 400 AN: 3210

Other (OTH) AF: 0.155 AC: 46 AN: 296

GnomAD4 genome AF: 0.187 AC: 28484 AN: 152234 Hom.: 3368 Cov.: 34 AF XY: 0.186 AC XY: 13863 AN XY: 74422

African (AFR) AF: 0.319 AC: 13256 AN: 41524

American (AMR) AF: 0.0921 AC: 1408 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 605 AN: 3466

East Asian (EAS) AF: 0.0754 AC: 392 AN: 5196

South Asian (SAS) AF: 0.291 AC: 1402 AN: 4826

European-Finnish (FIN) AF: 0.128 AC: 1351 AN: 10592

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9545 AN: 68018

Other (OTH) AF: 0.161 AC: 340 AN: 2112

Alfa AF: 0.156 Hom.: 6782

Bravo AF: 0.186

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.57
PhyloP100		0.051
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: rs1046889; hg19: chr17-80685511;