NM_033163.5:c.731G>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 1P and 1B. PP2BP4

The NM_033163.5(FGF8):c.731G>A(p.Arg244Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000113 in 1,591,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FGF8
NM_033163.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.71

Publications

1 publications found

Variant links:

Genes affected

FGF8 (HGNC:3686): (fibroblast growth factor 8) 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 is known to be a factor that supports androgen and anchorage independent growth of mammary tumor cells. Overexpression of this gene has been shown to increase tumor growth and angiogensis. The adult expression of this gene is restricted to testes and ovaries. Temporal and spatial pattern of this gene expression suggests its function as an embryonic epithelial factor. Studies of the mouse and chick homologs revealed roles in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination. The alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

FGF8 Gene-Disease associations (from GenCC):

hypogonadotropic hypogonadism 6 with or without anosmia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital heart disease
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
hypogonadotropic hypogonadism
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
holoprosencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FGF8 links:

ENSG00000308881 (HGNC:):

ENSG00000308881 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 12 curated pathogenic missense variants (we use a threshold of 10). The gene has 3 curated benign missense variants. Gene score misZ: 1.5674 (below the threshold of 3.09). Trascript score misZ: 1.0113 (below the threshold of 3.09). GenCC associations: The gene is linked to hypogonadotropic hypogonadism, holoprosencephaly, hypogonadotropic hypogonadism 6 with or without anosmia, Kallmann syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.34279478).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033163.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF8	NM_033163.5	MANE Select	c.731G>A	p.Arg244Gln	missense	Exon 6 of 6	NP_149353.1	P55075-4
FGF8	NM_033164.4		c.698G>A	p.Arg233Gln	missense	Exon 6 of 6	NP_149354.1	P55075-1
FGF8	NM_006119.6		c.644G>A	p.Arg215Gln	missense	Exon 5 of 5	NP_006110.1	P55075-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF8	ENST00000320185.7	TSL:1 MANE Select	c.731G>A	p.Arg244Gln	missense	Exon 6 of 6	ENSP00000321797.2	P55075-4
FGF8	ENST00000344255.8	TSL:1	c.698G>A	p.Arg233Gln	missense	Exon 6 of 6	ENSP00000340039.3	P55075-1
FGF8	ENST00000347978.2	TSL:1	c.644G>A	p.Arg215Gln	missense	Exon 5 of 5	ENSP00000321945.2	P55075-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000187

AC:

AN:

213390

AF XY:

0.0000173

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000328

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000316

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1439680

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

713804

show subpopulations

African (AFR)

AF:

0.0000602

AC:

AN:

33242

American (AMR)

AF:

0.0000243

AC:

AN:

41140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25450

East Asian (EAS)

AF:

0.00

AC:

AN:

39026

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82808

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4184

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1102500

Other (OTH)

AF:

0.00

AC:

AN:

59490

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

Eigen

Benign

0.15

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.54

MetaRNN

Benign

0.34

MetaSVM

Uncertain

-0.040

MutationAssessor

Benign

0.0

PhyloP100

3.7

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.77

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.015

Polyphen

0.90

Vest4

0.27

MutPred

0.35

Loss of MoRF binding (P = 0.0031)

MVP

0.54

MPC

2.1

ClinPred

0.50

GERP RS

3.8

Varity_R

0.49

gMVP

0.24

Mutation Taster

=84/16

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over