17-82727657-C-T

Position:

• chr17-82727657-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.*486C>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 0.309 in 154,594 control chromosomes in the GnomAD database, including 7,677 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 0.31 (7536 hom., cov: 33)
  • Exomes 𝑓: 0.33 (141 hom.)
• Consequence: FN3KRP NM_024619.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN3KRP	NM_024619.4	c.*486C>T		3_prime_UTR_variant	6/6	ENST00000269373.11
FN3KRP	NR_046408.2	n.1594C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN3KRP	ENST00000269373.11	c.*486C>T		3_prime_UTR_variant	6/6	1	NM_024619.4	P1
FN3KRP	ENST00000571594.1	c.53+490C>T		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46849 AN: 151994 Hom.: 7525 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.333 AC: 827 AN: 2482 Hom.: 141 Cov.: 0 AF XY: 0.340 AC XY: 435 AN XY: 1278

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.308 AC: 46900 AN: 152112 Hom.: 7536 Cov.: 33 AF XY: 0.310 AC XY: 23068 AN XY: 74374

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.361

Alfa AF: 0.335 Hom.: 17625

Bravo AF: 0.316

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.91
DANN	Benign	0.66

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: rs1046896; hg19: chr17-80685533;