NM_022158.4:c.900C>G

Variant names:

• chr17-82750725-C-G
• rs1056534
• NM_022158.4:c.900C>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_022158.4(FN3K):​c.900C>G​(p.Ser300Ser) 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
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022158.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3K	NM_022158.4	MANE Select	c.900C>G	p.Ser300Ser	synonymous	Exon 6 of 6	NP_071441.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FN3K	ENST00000300784.8	TSL:1 MANE Select	c.900C>G	p.Ser300Ser	synonymous	Exon 6 of 6	ENSP00000300784.7
	FN3K	ENST00000910354.1		c.930C>G	p.Ser310Ser	synonymous	Exon 6 of 6	ENSP00000580413.1
	FN3K	ENST00000910355.1		c.921C>G	p.Ser307Ser	synonymous	Exon 6 of 6	ENSP00000580414.1

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

GnomAD2 exomes AF: 0.618 AC: 154749 AN: 250364 AF XY: 0.620

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 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

African (AFR) AF: 0.658 AC: 22029 AN: 33478

American (AMR) AF: 0.581 AC: 25977 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 16491 AN: 26122

East Asian (EAS) AF: 0.616 AC: 24453 AN: 39700

South Asian (SAS) AF: 0.647 AC: 55829 AN: 86254

European-Finnish (FIN) AF: 0.610 AC: 32243 AN: 52862

Middle Eastern (MID) AF: 0.612 AC: 3524 AN: 5762

European-Non Finnish (NFE) AF: 0.606 AC: 674006 AN: 1111868

Other (OTH) AF: 0.616 AC: 37175 AN: 60384

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

African (AFR) AF: 0.654 AC: 27058 AN: 41342

American (AMR) AF: 0.592 AC: 9040 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2171 AN: 3466

East Asian (EAS) AF: 0.621 AC: 3170 AN: 5104

South Asian (SAS) AF: 0.643 AC: 3084 AN: 4794

European-Finnish (FIN) AF: 0.608 AC: 6419 AN: 10564

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41583 AN: 67854

Other (OTH) AF: 0.626 AC: 1319 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.88
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		4.0
Mutation Taster		=100/0	polymorphism (auto)

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