Genetic Variant FGF5:p.His113Gln (chr4-80267163-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004464.4(FGF5):c.339C>A(p.His113Gln) variant causes a missense 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

FGF5
NM_004464.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.12

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

familial isolated trichomegaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
trichomegaly
Inheritance: AR Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

FGF5 links:

ENSG00000307236 (HGNC:):

ENSG00000307236 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22810304).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004464.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF5	NM_004464.4	MANE Select	c.339C>A	p.His113Gln	missense	Exon 1 of 3	NP_004455.2	P12034-1
	FGF5	NM_033143.2		c.339C>A	p.His113Gln	missense	Exon 1 of 2	NP_149134.1	Q8NBG6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGF5	ENST00000312465.12	TSL:1 MANE Select	c.339C>A	p.His113Gln	missense	Exon 1 of 3	ENSP00000311697.7	P12034-1
FGF5	ENST00000456523.3	TSL:1	c.339C>A	p.His113Gln	missense	Exon 1 of 2	ENSP00000398353.3	P12034-2
FGF5	ENST00000380628.3	TSL:1	n.339C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.034

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.044

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.69

M_CAP

Benign

0.071

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.4

PhyloP100

1.1

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.29

Sift

Benign

0.18

Sift4G

Uncertain

0.048

Polyphen

0.0030

Vest4

0.36

MutPred

0.42

Gain of solvent accessibility (P = 0.0766)

MVP

0.74

MPC

0.13

ClinPred

0.89

GERP RS

3.8

PromoterAI

0.014

Neutral

(source)

Varity_R

0.80

gMVP

0.38

Mutation Taster

=14/86

disease causing

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over