Genetic Variant NM_005247.4:c.673G>T (chr11-69810352-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_005247.4(FGF3):c.673G>T(p.Val225Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,414,410 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FGF3
NM_005247.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.94

Variant links:

Genes affected

FGF3 (HGNC:3681): (fibroblast growth factor 3) 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 gene was identified by its similarity with mouse fgf3/int-2, a proto-oncogene activated in virally induced mammary tumors in the mouse. Frequent amplification of this gene has been found in human tumors, which may be important for neoplastic transformation and tumor progression. Studies of the similar genes in mouse and chicken suggested the role in inner ear formation. [provided by RefSeq, Jul 2008]

FGF3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a chain Fibroblast growth factor 3 (size 221) in uniprot entity FGF3_HUMAN there are 12 pathogenic changes around while only 1 benign (92%) in NM_005247.4

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0651719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF3	NM_005247.4 link	c.673G>T	p.Val225Phe	missense_variant	Exon 3 of 3	ENST00000334134.4	NP_005238.1	P11487A0A7U3JVY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF3	ENST00000334134.4 link	c.673G>T	p.Val225Phe	missense_variant	Exon 3 of 3	1	NM_005247.4	ENSP00000334122.2		P11487
FGF3	ENST00000646078.1 link	n.520G>T		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000195

AC:

AN:

204986

Hom.:

AF XY:

0.00000893

AC XY:

AN XY:

111968

show subpopulations

Gnomad AFR exome

AF:

0.000163

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:

0.0000220

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1414410

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

696270

show subpopulations

Gnomad4 AFR exome

AF:

0.0000309

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:

9.23e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.50

CADD

Benign

1.2

DANN

Benign

0.87

DEOGEN2

Benign

0.37

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.38

M_CAP

Benign

0.012

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.45

REVEL

Benign

0.15

Sift

Uncertain

0.010

Sift4G

Uncertain

0.016

Polyphen

0.13

Vest4

0.17

MutPred

0.14

Loss of MoRF binding (P = 0.0845);

MVP

0.87

MPC

0.51

ClinPred

0.11

GERP RS

-3.0

Varity_R

0.047

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over