rs13955

Variant names:

• chr17-82726978-T-C
• rs13955
• NM_024619.4:c.737T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-82726978-T-C
• chr17-82726978-T-G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_024619.4(FN3KRP):​c.737T>C​(p.Leu246Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FN3KRP NM_024619.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.83
• Publications: 2 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

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.737T>C	p.Leu246Pro	missense	Exon 6 of 6	NP_078895.2
	FN3KRP	NR_046408.2		n.915T>C		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3KRP	ENST00000269373.11	TSL:1 MANE Select	c.737T>C	p.Leu246Pro	missense	Exon 6 of 6	ENSP00000269373.6	Q9HA64
	FN3KRP	ENST00000576363.1	TSL:1	n.547T>C		non_coding_transcript_exon	Exon 3 of 3
	FN3KRP	ENST00000910132.1		c.410T>C	p.Leu137Pro	missense	Exon 3 of 3	ENSP00000580191.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Pathogenic	4.3	H
PhyloP100		7.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.87		Gain of disorder (P = 0.0101)
MVP		0.85
MPC		0.58
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.98
gMVP		0.99

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

Other links and lift over

dbSNP: rs13955; hg19: chr17-80684854;