rs1046889

chr17-82727635-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN3KRP	NM_024619.4	c.*464C>T		3_prime_UTR_variant	6/6	ENST00000269373.11
FN3KRP	NR_046408.2	n.1572C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN3KRP	ENST00000269373.11	c.*464C>T		3_prime_UTR_variant	6/6	1	NM_024619.4	P1
FN3KRP	ENST00000571594.1	c.53+468C>T		intron_variant, NMD_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.0647

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.0676

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.155

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

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.0921

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0754

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.161

Alfa AF: 0.150 Hom.: 2641

Bravo AF: 0.186

Asia WGS AF: 0.199 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.8
Dann	Benign	0.57

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: rs1046889; hg19: chr17-80685511;