NM_004464.4:c.243G>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004464.4(FGF5):c.243G>T(p.Trp81Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00193 in 1,614,240 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 4 hom. )

Consequence

FGF5
NM_004464.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.56

Variant links:

Genes affected

FGF5 (HGNC:3683): (fibroblast growth factor 5) 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 as an oncogene, which confers transforming potential when transfected into mammalian cells. Targeted disruption of the homolog of this gene in mouse resulted in the phenotype of abnormally long hair, which suggested a function as an inhibitor of hair elongation. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FGF5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019742876).

BP6

Variant 4-80267067-G-T is Benign according to our data. Variant chr4-80267067-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 786515.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF5	NM_004464.4 link	c.243G>T	p.Trp81Cys	missense_variant	Exon 1 of 3	ENST00000312465.12	NP_004455.2	P12034-1Q8NBG6A0A7U3L5M4
FGF5	NM_033143.2 link	c.243G>T	p.Trp81Cys	missense_variant	Exon 1 of 2		NP_149134.1	P12034-2Q8NBG6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGF5	ENST00000312465.12 link	c.243G>T	p.Trp81Cys	missense_variant	Exon 1 of 3	1	NM_004464.4	ENSP00000311697.7	P12034-1
FGF5	ENST00000456523.3 link	c.243G>T	p.Trp81Cys	missense_variant	Exon 1 of 2	1		ENSP00000398353.3	P12034-2
FGF5	ENST00000380628.3 link	n.243G>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
FGF5	ENST00000507780.1 link	n.126G>T		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000423903.1	H0Y9E2

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00288

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00169

AC:

424

AN:

251104

Hom.:

AF XY:

0.00158

AC XY:

215

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00106

Gnomad NFE exome

AF:

0.00339

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00197

AC:

2887

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

1424

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00247

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152376

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00288

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00231

Hom.:

Bravo

AF:

0.00136

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00208

AC:

252

EpiCase

AF:

0.00174

EpiControl

AF:

0.00237

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FGF5-related disorder

Benign:1

Feb 26, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.84

D;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0050

D;D

Sift4G

Benign

0.067

T;D

Polyphen

0.99

D;D

Vest4

0.60

MutPred

0.43

Loss of MoRF binding (P = 0.0198);Loss of MoRF binding (P = 0.0198);

MVP

0.74

MPC

0.52

ClinPred

0.073

GERP RS

5.4

Varity_R

0.28

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over