17-82750725-C-G

Position:

• chr17-82750725-C-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022158.4(FN3K):​c.900C>G​(p.Ser300=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,612,850 control chromosomes in the GnomAD database, including 302,159 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 0.62 (29574 hom., cov: 29)
  • Exomes 𝑓: 0.61 (272585 hom.)
• Consequence: FN3K NM_022158.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882

Genes affected

FN3K (HGNC:24822): (fructosamine 3 kinase) 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, fructosamines, are less active or functional. This gene encodes an enzyme which catalyzes the phosphorylation of fructosamines which may result in deglycation. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.882 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FN3K	NM_022158.4	c.900C>G	p.Ser300=	synonymous_variant	6/6	ENST00000300784.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FN3K	ENST00000300784.8	c.900C>G	p.Ser300=	synonymous_variant	6/6	1	NM_022158.4	P1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94487 AN: 151580 Hom.: 29518 Cov.: 29

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.622

GnomAD3 exomes AF: 0.618 AC: 154749 AN: 250364 Hom.: 48024 AF XY: 0.620 AC XY: 84053 AN XY: 135524

Gnomad AFR exome AF: 0.657

Gnomad AMR exome AF: 0.581

Gnomad ASJ exome AF: 0.623

Gnomad EAS exome AF: 0.631

Gnomad SAS exome AF: 0.650

Gnomad FIN exome AF: 0.611

Gnomad NFE exome AF: 0.614

Gnomad OTH exome AF: 0.614

GnomAD4 exome AF: 0.610 AC: 891727 AN: 1461150 Hom.: 272585 Cov.: 55 AF XY: 0.612 AC XY: 444872 AN XY: 726902

Gnomad4 AFR exome AF: 0.658

Gnomad4 AMR exome AF: 0.581

Gnomad4 ASJ exome AF: 0.631

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.647

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.606

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.624 AC: 94604 AN: 151700 Hom.: 29574 Cov.: 29 AF XY: 0.624 AC XY: 46281 AN XY: 74128

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.643

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.626

Alfa AF: 0.622 Hom.: 9539

Bravo AF: 0.621

Asia WGS AF: 0.648 AC: 2252 AN: 3478

EpiCase AF: 0.612

EpiControl AF: 0.605

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.66
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		4.0

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

LitVar

Other links and lift over

dbSNP: rs1056534; hg19: chr17-80708601; COSMIC: COSV56181328; COSMIC: COSV56181328;