17-82716834-C-G

Variant names:

• chr17-82716834-C-G
• rs200062745
• NM_024619.4:c.79C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024619.4(FN3KRP):​c.79C>G​(p.Gln27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000513 in 1,559,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FN3KRP NM_024619.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.30
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064254075).

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.79C>G	p.Gln27Glu	missense	Exon 1 of 6	NP_078895.2
	FN3KRP	NR_046408.2		n.129C>G		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3KRP	ENST00000269373.11	TSL:1 MANE Select	c.79C>G	p.Gln27Glu	missense	Exon 1 of 6	ENSP00000269373.6	Q9HA64
	FN3KRP	ENST00000910132.1		c.79C>G	p.Gln27Glu	missense	Exon 1 of 3	ENSP00000580191.1
	FN3KRP	ENST00000577128.1	TSL:5	c.-72C>G		5_prime_UTR	Exon 1 of 5	ENSP00000459653.1	I3L2G3

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152178 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000102 AC: 2 AN: 196224 AF XY: 0.00000917

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000811

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1406842 Hom.: 0 Cov.: 50 AF XY: 0.00 AC XY: 0 AN XY: 699528

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28818

American (AMR) AF: 0.0000569 AC: 2 AN: 35124

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24604

East Asian (EAS) AF: 0.00 AC: 0 AN: 32646

South Asian (SAS) AF: 0.00 AC: 0 AN: 80152

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 9.18e-7 AC: 1 AN: 1089772

Other (OTH) AF: 0.00 AC: 0 AN: 58014

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000888178), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152288 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.000261 AC: 4 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.0000567

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.85	T
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.30	N
PhyloP100		2.3
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.11
Sift	Benign	0.68	T
Sift4G	Benign	0.74	T
Polyphen		0.0010	B
Vest4		0.11
MVP		0.38
MPC		0.095
ClinPred		0.23	T
GERP RS		4.3
PromoterAI		-0.011	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.7
Varity_R		0.39
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs200062745; hg19: chr17-80674710;