dbSNP rs281860301: FGF3:p.Cys50Cys (chr11-69818784-G-A) – 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.150C>T(p.Cys50Cys) 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.

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: 2.47

Publications

3 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, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

FGF3 links:

LOC107984368 (HGNC:):

LOC107984368 links:

Genome browser will be placed here

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=-0.52).

BP7

Synonymous conserved (PhyloP=2.47 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF3	NM_005247.4 link	c.150C>T	p.Cys50Cys	synonymous_variant	Exon 1 of 3	ENST00000334134.4	NP_005238.1	P11487A0A7U3JVY0
LOC107984368	XR_001748071.2 link	n.77G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF3	ENST00000334134.4 link	c.150C>T	p.Cys50Cys	synonymous_variant	Exon 1 of 3	1	NM_005247.4	ENSP00000334122.2		P11487
ENSG00000300527	ENST00000772585.1 link	n.-187G>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000991

AC:

AN:

100878

AF XY:

0.0000177

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000262

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1343574

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

663178

African (AFR)

AF:

0.00

AC:

AN:

27342

American (AMR)

AF:

0.00

AC:

AN:

30716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23702

East Asian (EAS)

AF:

0.00

AC:

AN:

30806

South Asian (SAS)

AF:

0.00

AC:

AN:

75236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4434

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061386

Other (OTH)

AF:

0.00

AC:

AN:

55756

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

2.5

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over