chr8-16993092-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019851.3(FGF20):​c.616G>A​(p.Asp206Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,613,932 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D206Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.022 ( 110 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 105 hom. )

Consequence

FGF20
NM_019851.3 missense

Scores

4
6
8

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.57
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.003193587).
BP6
Variant 8-16993092-C-T is Benign according to our data. Variant chr8-16993092-C-T is described in ClinVar as [Benign]. Clinvar id is 784125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGF20NM_019851.3 linkuse as main transcriptc.616G>A p.Asp206Asn missense_variant 3/3 ENST00000180166.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGF20ENST00000180166.6 linkuse as main transcriptc.616G>A p.Asp206Asn missense_variant 3/31 NM_019851.3 P1
FGF20ENST00000519941.1 linkuse as main transcriptc.322G>A p.Asp108Asn missense_variant 2/25

Frequencies

GnomAD3 genomes
AF:
0.0219
AC:
3330
AN:
152058
Hom.:
110
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0752
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00977
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000368
Gnomad OTH
AF:
0.0186
GnomAD3 exomes
AF:
0.00578
AC:
1452
AN:
251328
Hom.:
46
AF XY:
0.00437
AC XY:
594
AN XY:
135842
show subpopulations
Gnomad AFR exome
AF:
0.0746
Gnomad AMR exome
AF:
0.00483
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000405
Gnomad OTH exome
AF:
0.00277
GnomAD4 exome
AF:
0.00240
AC:
3507
AN:
1461756
Hom.:
105
Cov.:
31
AF XY:
0.00207
AC XY:
1508
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.0774
Gnomad4 AMR exome
AF:
0.00543
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000290
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000237
Gnomad4 OTH exome
AF:
0.00596
GnomAD4 genome
AF:
0.0219
AC:
3334
AN:
152176
Hom.:
110
Cov.:
32
AF XY:
0.0213
AC XY:
1582
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.0751
Gnomad4 AMR
AF:
0.00975
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000368
Gnomad4 OTH
AF:
0.0184
Alfa
AF:
0.00411
Hom.:
46
Bravo
AF:
0.0251
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.0683
AC:
301
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.00700
AC:
850
Asia WGS
AF:
0.00664
AC:
23
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 19, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.36
T
Eigen
Uncertain
0.61
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D
MetaRNN
Benign
0.0032
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.6
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.0
N
REVEL
Uncertain
0.47
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.87
P
Vest4
0.51
MVP
0.80
MPC
0.011
ClinPred
0.026
T
GERP RS
5.8
Varity_R
0.65
gMVP
0.63

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17550360; hg19: chr8-16850601; API