chr17-82720282-A-C

Position:

• chr17-82720282-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024619.4(FN3KRP):​c.304A>C​(p.Lys102Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FN3KRP NM_024619.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08734876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN3KRP	NM_024619.4	c.304A>C	p.Lys102Gln	missense_variant	3/6	ENST00000269373.11
FN3KRP	NR_046408.2	n.482A>C		non_coding_transcript_exon_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN3KRP	ENST00000269373.11	c.304A>C	p.Lys102Gln	missense_variant	3/6	1	NM_024619.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.304A>C (p.K102Q) alteration is located in exon 3 (coding exon 3) of the FN3KRP gene. This alteration results from a A to C substitution at nucleotide position 304, causing the lysine (K) at amino acid position 102 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.86
DEOGEN2	Benign	0.0022	T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.70
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.37	N;.
MutationTaster	Benign	0.50	D;D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.52	N;.
REVEL	Benign	0.023
Sift	Benign	0.47	T;.
Sift4G	Benign	0.57	T;T
Polyphen		0.0020	B;.
Vest4		0.26
MutPred		0.38		Loss of ubiquitination at K102 (P = 0.0134);.;
MVP		0.32
MPC		0.090
ClinPred		0.060	T
GERP RS		1.9
Varity_R		0.069
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-80678158;