13-21701807-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002010.3(FGF9):c.*372A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 275,282 control chromosomes in the GnomAD database, including 5,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3933 hom., cov: 31)

Exomes 𝑓: 0.12 ( 1176 hom. )

Consequence

FGF9
NM_002010.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.05

Publications

15 publications found

Variant links:

Genes affected

FGF9 (HGNC:3687): (fibroblast growth factor 9) 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 protein was isolated as a secreted factor that exhibits a growth-stimulating effect on cultured glial cells. In nervous system, this protein is produced mainly by neurons and may be important for glial cell development. Expression of the mouse homolog of this gene was found to be dependent on Sonic hedgehog (Shh) signaling. Mice lacking the homolog gene displayed a male-to-female sex reversal phenotype, which suggested a role in testicular embryogenesis. [provided by RefSeq, Jul 2008]

FGF9 Gene-Disease associations (from GenCC):

multiple synostoses syndrome 3
Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
multiple synostoses syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FGF9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 13-21701807-A-T is Benign according to our data. Variant chr13-21701807-A-T is described in ClinVar as Benign. ClinVar VariationId is 311441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF9	NM_002010.3 link	c.*372A>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000382353.6	NP_002001.1	P31371A0A7U3L6D0
FGF9	XM_011534996.3 link	c.*372A>T		3_prime_UTR_variant	Exon 3 of 3		XP_011533298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF9	ENST00000382353.6 link	c.*372A>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_002010.3	ENSP00000371790.5		P31371
FGF9	ENST00000478546.1 link	n.759A>T		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29352

AN:

151362

Hom.:

3911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.105

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.0339

Gnomad SAS

AF:

0.0833

Gnomad FIN

AF:

0.160

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.132

Gnomad OTH

AF:

0.167

GnomAD4 exome

AF:

0.119

AC:

14731

AN:

123804

Hom.:

1176

Cov.:

AF XY:

0.114

AC XY:

7509

AN XY:

65706

show subpopulations

African (AFR)

AF:

0.362

AC:

1485

AN:

4102

American (AMR)

AF:

0.0687

AC:

413

AN:

6014

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

330

AN:

3214

East Asian (EAS)

AF:

0.0333

AC:

221

AN:

6644

South Asian (SAS)

AF:

0.0827

AC:

1547

AN:

18698

European-Finnish (FIN)

AF:

0.150

AC:

758

AN:

5042

Middle Eastern (MID)

AF:

0.0955

AC:

AN:

492

European-Non Finnish (NFE)

AF:

0.124

AC:

9087

AN:

72996

Other (OTH)

AF:

0.128

AC:

843

AN:

6602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

581

1163

1744

2326

2907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<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:

0.194

AC:

29433

AN:

151478

Hom.:

3933

Cov.:

AF XY:

0.191

AC XY:

14117

AN XY:

74002

show subpopulations

African (AFR)

AF:

0.383

AC:

15764

AN:

41166

American (AMR)

AF:

0.105

AC:

1600

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

384

AN:

3464

East Asian (EAS)

AF:

0.0336

AC:

173

AN:

5156

South Asian (SAS)

AF:

0.0836

AC:

400

AN:

4784

European-Finnish (FIN)

AF:

0.160

AC:

1681

AN:

10490

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.132

AC:

8965

AN:

67896

Other (OTH)

AF:

0.164

AC:

344

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1030

2060

3090

4120

5150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.133

Hom.:

912

Bravo

AF:

0.199

Asia WGS

AF:

0.0790

AC:

276

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Multiple synostoses syndrome 3

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

2.0

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

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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