4-80267163-C-A

Variant names:

• chr4-80267163-C-A
• rs373878896
• NM_004464.4:c.339C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FGF5 NM_004464.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22810304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF5	NM_004464.4	c.339C>A	p.His113Gln	missense_variant	Exon 1 of 3	ENST00000312465.12	NP_004455.2
FGF5	NM_033143.2	c.339C>A	p.His113Gln	missense_variant	Exon 1 of 2		NP_149134.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF5	ENST00000312465.12	c.339C>A	p.His113Gln	missense_variant	Exon 1 of 3	1	NM_004464.4	ENSP00000311697.7
FGF5	ENST00000456523.3	c.339C>A	p.His113Gln	missense_variant	Exon 1 of 2	1		ENSP00000398353.3
FGF5	ENST00000380628.3	n.339C>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
FGF5	ENST00000507780.1	n.222C>A		non_coding_transcript_exon_variant	Exon 1 of 5	3		ENSP00000423903.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.79	D;.
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.29
Sift	Benign	0.18	T;D
Sift4G	Uncertain	0.048	D;D
Polyphen		0.0030	B;P
Vest4		0.36
MutPred		0.42		Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);
MVP		0.74
MPC		0.13
ClinPred		0.89	D
GERP RS		3.8
Varity_R		0.80
gMVP		0.38

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

Other links and lift over

dbSNP: rs373878896; hg19: chr4-81188317;