Genetic Variant FN3KRP:c.*486C>T (chr17-82727657-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.21

Publications

65 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
FN3KRP	NM_024619.4 link	c.*486C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000269373.11	NP_078895.2	Q9HA64A0A140VK84
FN3KRP	NR_046408.2 link	n.1594C>T		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FN3KRP	ENST00000269373.11 link	c.*486C>T	3_prime_UTR_variant	Exon 6 of 6	1	NM_024619.4	ENSP00000269373.6	Q9HA64
FN3KRP	ENST00000571594.1 link	n.53+490C>T	intron_variant	Intron 1 of 2	3		ENSP00000459751.1	I3L2K8
FN3KRP	ENST00000574832.5 link	n.*1373C>T	downstream_gene_variant		2		ENSP00000460869.1	I3L407

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46849

AN:

151994

Hom.:

7525

Cov.:

show subpopulations

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.:

AF XY:

0.340

AC XY:

435

AN XY:

1278

show subpopulations

African (AFR)

AF:

0.208

AC:

AN:

American (AMR)

AF:

0.424

AC:

140

AN:

330

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.389

AC:

AN:

European-Finnish (FIN)

AF:

0.233

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.315

AC:

523

AN:

1660

Other (OTH)

AF:

0.296

AC:

AN:

142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

117

146

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.308

AC:

46900

AN:

152112

Hom.:

7536

Cov.:

AF XY:

0.310

AC XY:

23068

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.236

AC:

9805

AN:

41478

American (AMR)

AF:

0.388

AC:

5935

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1270

AN:

3472

East Asian (EAS)

AF:

0.496

AC:

2567

AN:

5174

South Asian (SAS)

AF:

0.387

AC:

1865

AN:

4820

European-Finnish (FIN)

AF:

0.264

AC:

2793

AN:

10594

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.317

AC:

21553

AN:

67982

Other (OTH)

AF:

0.361

AC:

760

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1660

3321

4981

6642

8302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.325

Hom.:

35624

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

(source)

DANN

Benign

0.66

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over