Genetic Variant FGF3:p.Ala23Ala (chr11-69818865-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_005247.4(FGF3):c.69G>A(p.Ala23Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A23A) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FGF3
NM_005247.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.236

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

deafness with labyrinthine aplasia, microtia, and microdontia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

FGF3 links:

LOC107984368 (HGNC:):

LOC107984368 links:

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new If you want to explore the variant's impact on the transcript NM_005247.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-0.236 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005247.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF3	NM_005247.4	MANE Select	c.69G>A	p.Ala23Ala	synonymous	Exon 1 of 3	NP_005238.1	P11487

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF3	ENST00000334134.4	TSL:1 MANE Select	c.69G>A	p.Ala23Ala	synonymous	Exon 1 of 3	ENSP00000334122.2	P11487
	ENSG00000300527	ENST00000772585.1		n.-106C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1308934

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

645856

African (AFR)

AF:

0.00

AC:

AN:

26114

American (AMR)

AF:

0.00

AC:

AN:

23894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22546

East Asian (EAS)

AF:

0.00

AC:

AN:

28502

South Asian (SAS)

AF:

0.00

AC:

AN:

71356

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3912

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1045382

Other (OTH)

AF:

0.00

AC:

AN:

53950

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

8.2

(source)

DANN

Benign

0.83

PhyloP100

-0.24

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over