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rs104894393

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5

The NM_004115.4(FGF14):c.434T>C(p.Phe145Ser) 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. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

FGF14
NM_004115.4 missense

Scores

16
1

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 8.95
Variant links:
Genes affected
FGF14 (HGNC:3671): (fibroblast growth factor 14) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members 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. A mutation in this gene is associated with autosomal dominant cerebral ataxia. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.991
PP5
Variant 13-101726785-A-G is Pathogenic according to our data. Variant chr13-101726785-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 8115.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr13-101726785-A-G is described in Lovd as [Pathogenic]. Variant chr13-101726785-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FGF14NM_004115.4 linkuse as main transcriptc.434T>C p.Phe145Ser missense_variant 4/5 ENST00000376143.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FGF14ENST00000376143.5 linkuse as main transcriptc.434T>C p.Phe145Ser missense_variant 4/51 NM_004115.4 P2Q92915-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Spinocerebellar ataxia 27A Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 01, 2003- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.39
Cadd
Pathogenic
31
Dann
Pathogenic
1.0
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
0.97
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D;D
M_CAP
Pathogenic
0.47
D
MetaRNN
Pathogenic
0.99
D;D
MetaSVM
Pathogenic
0.82
D
MutationTaster
Benign
1.0
A;A
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-6.8
D;D
REVEL
Pathogenic
0.92
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
1.0
MutPred
0.97
.;Gain of disorder (P = 5e-04);
MVP
0.98
MPC
2.5
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.97
gMVP
0.97

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: rs104894393; hg19: chr13-102379135; API