rs1046875

chr17-82727550-A-G

Variant summary

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

The NM_024619.4(FN3KRP):c.*379A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 187,428 control chromosomes in the GnomAD database, including 43,654 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 0.69 (36008 hom., cov: 34)
  • Exomes 𝑓: 0.65 (7646 hom.)
• Consequence: FN3KRP NM_024619.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.52

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN3KRP	NM_024619.4	c.*379A>G		3_prime_UTR_variant	6/6	ENST00000269373.11
FN3KRP	NR_046408.2	n.1487A>G		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN3KRP	ENST00000269373.11	c.*379A>G		3_prime_UTR_variant	6/6	1	NM_024619.4	P1
FN3KRP	ENST00000571594.1	c.53+383A>G		intron_variant, NMD_transcript_variant		3
FN3KRP	ENST00000574832.5			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104235 AN: 152022 Hom.: 35990 Cov.: 34

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.644

GnomAD4 exome AF: 0.649 AC: 22910 AN: 35288 Hom.: 7646 Cov.: 0 AF XY: 0.645 AC XY: 11876 AN XY: 18404

Gnomad4 AFR exome AF: 0.716

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.630

Gnomad4 EAS exome AF: 0.493

Gnomad4 SAS exome AF: 0.608

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.686 AC: 104300 AN: 152140 Hom.: 36008 Cov.: 34 AF XY: 0.684 AC XY: 50860 AN XY: 74378

Gnomad4 AFR AF: 0.742

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.683

Gnomad4 OTH AF: 0.638

Alfa AF: 0.665 Hom.: 43974

Bravo AF: 0.677

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.13
Dann	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs1046875; hg19: chr17-80685426;