rs398123026

chr8-22048158-A-Cchr8-22048158-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_003867.4(FGF17):c.560A>C(p.Asn187Thr) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. N187S) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGF17 NM_003867.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32

Genes affected

FGF17 (HGNC:3673): (fibroblast growth factor 17) This gene encodes a member of the fibroblast growth factor (FGF) family. Member of the FGF family 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 expressed during embryogenesis and in the adult cerebellum and cortex and may be essential for vascular growth and normal brain development. Mutations in this gene are the cause of hypogonadotropic hypogonadism 20 with or without anosmia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr8-22048158-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 50860.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.18080992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF17	NM_003867.4	c.560A>C	p.Asn187Thr	missense_variant	5/5	ENST00000359441.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF17	ENST00000359441.4	c.560A>C	p.Asn187Thr	missense_variant	5/5	1	NM_003867.4	P4
FGF17	ENST00000518533.5	c.527A>C	p.Asn176Thr	missense_variant	5/5	1		A1
FGF17	ENST00000521709.1	n.798A>C		non_coding_transcript_exon_variant	3/3	3
FGF17	ENST00000524314.1	n.1930A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Benign	0.012
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.53	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.35	N;N
REVEL	Uncertain	0.31
Sift	Benign	0.35	T;T
Sift4G	Benign	0.23	T;T
Polyphen		0.13	B;P
Vest4		0.31
MutPred		0.19		.;Loss of solvent accessibility (P = 0.0193);
MVP		0.80
MPC		1.9
ClinPred		0.89	D
GERP RS		4.9
Varity_R		0.30
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-21905669; COSMIC: COSV100846131; COSMIC: COSV100846131;