NM_005247.4:c.69G>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005247.4(FGF3):c.69G>T(p.Ala23Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,460,720 control chromosomes in the GnomAD database, including 8,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.098 ( 789 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7230 hom. )

Consequence

FGF3
NM_005247.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.236

Publications

6 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: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 11-69818865-C-A is Benign according to our data. Variant chr11-69818865-C-A is described in ClinVar as Benign. ClinVar VariationId is 259690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF3	NM_005247.4 link	c.69G>T	p.Ala23Ala	synonymous_variant	Exon 1 of 3	ENST00000334134.4	NP_005238.1
LOC107984368	XR_001748071.2 link	n.158C>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.69G>T	p.Ala23Ala	synonymous_variant	Exon 1 of 3	1	NM_005247.4	ENSP00000334122.2
ENSG00000300527	ENST00000772585.1 link	n.-106C>A		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0985

AC:

14943

AN:

151716

Hom.:

791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.115

Gnomad AMI

AF:

0.0791

Gnomad AMR

AF:

0.0514

Gnomad ASJ

AF:

0.0404

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.0904

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0874

GnomAD2 exomes

AF:

0.0899

AC:

6822

AN:

75870

AF XY:

0.0913

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.0452

Gnomad ASJ exome

AF:

0.0368

Gnomad EAS exome

AF:

0.0173

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.0816

GnomAD4 exome

AF:

0.102

AC:

133292

AN:

1308894

Hom.:

7230

Cov.:

AF XY:

0.102

AC XY:

65743

AN XY:

645836

show subpopulations

African (AFR)

AF:

0.119

AC:

3096

AN:

26114

American (AMR)

AF:

0.0457

AC:

1092

AN:

23892

Ashkenazi Jewish (ASJ)

AF:

0.0415

AC:

936

AN:

22546

East Asian (EAS)

AF:

0.0203

AC:

579

AN:

28502

South Asian (SAS)

AF:

0.0947

AC:

6760

AN:

71354

European-Finnish (FIN)

AF:

0.121

AC:

4029

AN:

33278

Middle Eastern (MID)

AF:

0.0465

AC:

182

AN:

3912

European-Non Finnish (NFE)

AF:

0.107

AC:

111882

AN:

1045348

Other (OTH)

AF:

0.0878

AC:

4736

AN:

53948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

6341

12681

19022

25362

31703

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4160

8320

12480

16640

20800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0984

AC:

14946

AN:

151826

Hom.:

789

Cov.:

AF XY:

0.0981

AC XY:

7279

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.115

AC:

4763

AN:

41450

American (AMR)

AF:

0.0513

AC:

783

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.0404

AC:

140

AN:

3468

East Asian (EAS)

AF:

0.0158

AC:

AN:

5118

South Asian (SAS)

AF:

0.0909

AC:

439

AN:

4832

European-Finnish (FIN)

AF:

0.109

AC:

1149

AN:

10514

Middle Eastern (MID)

AF:

0.0445

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.108

AC:

7324

AN:

67882

Other (OTH)

AF:

0.0865

AC:

182

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

710

1420

2131

2841

3551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.109

Hom.:

121

Bravo

AF:

0.0934

Asia WGS

AF:

0.0540

AC:

187

AN:

3438

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 26, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.3

(source)

DANN

Benign

0.49

PhyloP100

-0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over