17-82716772-G-T

Variant names:

• chr17-82716772-G-T
• NM_024619.4:c.17G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024619.4(FN3KRP):​c.17G>T​(p.Arg6Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000726 in 1,377,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FN3KRP NM_024619.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FN3KRP	NM_024619.4	c.17G>T	p.Arg6Met	missense_variant	Exon 1 of 6	ENST00000269373.11	NP_078895.2
FN3KRP	NR_046408.2	n.67G>T		non_coding_transcript_exon_variant	Exon 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FN3KRP	ENST00000269373.11	c.17G>T	p.Arg6Met	missense_variant	Exon 1 of 6	1	NM_024619.4	ENSP00000269373.6

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.26e-7 AC: 1 AN: 1377046 Hom.: 0 Cov.: 50 AF XY: 0.00000146 AC XY: 1 AN XY: 683640

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.043	D
Polyphen		0.95	P
Vest4		0.20
MutPred		0.54		Loss of MoRF binding (P = 0.0797);
MVP		0.54
MPC		0.38
ClinPred		0.97	D
GERP RS		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-80674648;