Genetic Variant FN3KRP:p.Arg37Gly (chr17-82716864-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024619.4(FN3KRP):c.109C>G(p.Arg37Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000702 in 1,566,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Consequence

FN3KRP
NM_024619.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.68

Publications

0 publications found

Variant links:

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]

FN3KRP links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20884204).

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.109C>G	p.Arg37Gly	missense	Exon 1 of 6	NP_078895.2
	FN3KRP	NR_046408.2		n.159C>G		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FN3KRP	ENST00000269373.11	TSL:1 MANE Select	c.109C>G	p.Arg37Gly	missense	Exon 1 of 6	ENSP00000269373.6	Q9HA64
FN3KRP	ENST00000910132.1		c.109C>G	p.Arg37Gly	missense	Exon 1 of 3	ENSP00000580191.1
FN3KRP	ENST00000577128.1	TSL:5	c.-42C>G		5_prime_UTR	Exon 1 of 5	ENSP00000459653.1	I3L2G3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

GnomAD2 exomes

AF:

0.0000394

AC:

AN:

203122

AF XY:

0.0000356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000300

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:

0.00000707

AC:

AN:

1414338

Hom.:

Cov.:

AF XY:

0.00000711

AC XY:

AN XY:

703350

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29042

American (AMR)

AF:

0.000268

AC:

AN:

37368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24770

East Asian (EAS)

AF:

0.00

AC:

AN:

33188

South Asian (SAS)

AF:

0.00

AC:

AN:

81200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5656

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092604

Other (OTH)

AF:

0.00

AC:

AN:

58388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41446

American (AMR)

AF:

0.0000654

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000331

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.050

Eigen

Benign

0.064

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

2.9

PhyloP100

2.7

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.19

Sift

Benign

0.15

Sift4G

Benign

0.29

Polyphen

0.22

Vest4

0.22

MutPred

0.61

Loss of MoRF binding (P = 0.0053)

MVP

0.45

MPC

0.17

ClinPred

0.32

GERP RS

5.3

PromoterAI

-0.088

Neutral

(source)

Varity_R

0.79

gMVP

0.78

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over