chr8-16993125-C-A

Variant names:

• chr8-16993125-C-A
• rs1212546905
• NM_019851.3:c.583G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_019851.3(FGF20):​c.583G>T​(p.Val195Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGF20 NM_019851.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

Genes affected

FGF20 (HGNC:3677): (fibroblast growth factor 20) The protein encoded by this gene is a member of the fibroblast growth factor family. The fibroblast growth factors possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene product is a secreted neurotrophic factor but lacks a typical signal peptide. It is expressed in normal brain, particularly the cerebellum, and may regulate central nervous system development and function. Homodimerization of this protein was shown to regulate its receptor binding activity and concentration gradient in the extracellular matrix. Genetic variations of this gene have been associated with Parkinson disease susceptibility. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF20	NM_019851.3	c.583G>T	p.Val195Leu	missense_variant	Exon 3 of 3	ENST00000180166.6	NP_062825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF20	ENST00000180166.6	c.583G>T	p.Val195Leu	missense_variant	Exon 3 of 3	1	NM_019851.3	ENSP00000180166.5
FGF20	ENST00000519941.1	c.286G>T	p.Val96Leu	missense_variant	Exon 2 of 2	5		ENSP00000428072.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.27
Sift	Benign	0.074	T
Sift4G	Uncertain	0.053	T
Polyphen		0.62	P
Vest4		0.65
MutPred		0.36		Gain of helix (P = 0.0496);
MVP		0.70
MPC		0.020
ClinPred		0.96	D
GERP RS		5.8
Varity_R		0.58
gMVP		0.64

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: rs1212546905; hg19: chr8-16850634;