Variant 3-192144014-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004113.6(FGF12):c.541A>G(p.Thr181Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000009 in 1,443,724 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

FGF12
NM_004113.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.89

Variant links:

Genes affected

FGF12 (HGNC:3668): (fibroblast growth factor 12) 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. This growth factor lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, this protein accumulated in the nucleus, but was not secreted. The specific function of this gene has not yet been determined. [provided by RefSeq, Dec 2019]

FGF12 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19705248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6 linkuse as main transcript	c.541A>G	p.Thr181Ala	missense_variant	6/6	ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7 linkuse as main transcript	c.541A>G	p.Thr181Ala	missense_variant	6/6	1	NM_004113.6	A1	P61328-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251194

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000900

AC:

AN:

1443724

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719570

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000100

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 21, 2023

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2195318). This variant has not been reported in the literature in individuals affected with FGF12-related conditions. This variant is present in population databases (rs780659108, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 243 of the FGF12 protein (p.Thr243Ala). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.18

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.075

MetaRNN

Benign

0.20

T;T;T;T

MetaSVM

Uncertain

-0.049

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.92

N;N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.023

D;D;D;D

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

0.99

D;P;D;.

Vest4

0.17

MVP

0.84

MPC

1.4

ClinPred

0.46

GERP RS

4.7

Varity_R

0.13

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over