rs1046875

Variant names:

• chr17-82727550-A-G
• rs1046875
• NM_024619.4:c.*379A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 41 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3KRP	NM_024619.4	MANE Select	c.*379A>G		3_prime_UTR	Exon 6 of 6	NP_078895.2
	FN3KRP	NR_046408.2		n.1487A>G		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3KRP	ENST00000269373.11	TSL:1 MANE Select	c.*379A>G		3_prime_UTR	Exon 6 of 6	ENSP00000269373.6	Q9HA64
	FN3KRP	ENST00000910132.1		c.*379A>G		3_prime_UTR	Exon 3 of 3	ENSP00000580191.1
	FN3KRP	ENST00000571594.1	TSL:3	n.53+383A>G		intron	N/A	ENSP00000459751.1	I3L2K8

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

African (AFR) AF: 0.716 AC: 960 AN: 1340

American (AMR) AF: 0.572 AC: 1888 AN: 3302

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 670 AN: 1064

East Asian (EAS) AF: 0.493 AC: 1253 AN: 2540

South Asian (SAS) AF: 0.608 AC: 1337 AN: 2200

European-Finnish (FIN) AF: 0.750 AC: 996 AN: 1328

Middle Eastern (MID) AF: 0.642 AC: 86 AN: 134

European-Non Finnish (NFE) AF: 0.675 AC: 14523 AN: 21518

Other (OTH) AF: 0.643 AC: 1197 AN: 1862

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

African (AFR) AF: 0.742 AC: 30787 AN: 41496

American (AMR) AF: 0.609 AC: 9309 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2202 AN: 3472

East Asian (EAS) AF: 0.503 AC: 2603 AN: 5174

South Asian (SAS) AF: 0.614 AC: 2962 AN: 4826

European-Finnish (FIN) AF: 0.736 AC: 7802 AN: 10596

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.683 AC: 46435 AN: 67976

Other (OTH) AF: 0.638 AC: 1349 AN: 2116

Alfa AF: 0.674 Hom.: 109510

Bravo AF: 0.677

Asia WGS AF: 0.566 AC: 1969 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.13
DANN	Benign	0.35
PhyloP100		-4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
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: rs1046875; hg19: chr17-80685426;