5-142613988-T-C

Position:

• chr5-142613988-T-C

Variant summary

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

The NM_000800.5(FGF1):​c.140A>G​(p.Asp47Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FGF1 NM_000800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.97

Genes affected

FGF1 (HGNC:3665): (fibroblast growth factor 1) 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 functions as a modifier of endothelial cell migration and proliferation, as well as an angiogenic factor. It acts as a mitogen for a variety of mesoderm- and neuroectoderm-derived cells in vitro, thus is thought to be involved in organogenesis. Multiple alternatively spliced variants encoding different isoforms have been described. [provided by RefSeq, Jan 2009]

FGF1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF1	NM_000800.5	c.140A>G	p.Asp47Gly	missense_variant	2/4	ENST00000337706.7	NP_000791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF1	ENST00000337706.7	c.140A>G	p.Asp47Gly	missense_variant	2/4	2	NM_000800.5	ENSP00000338548.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.140A>G (p.D47G) alteration is located in exon 3 (coding exon 1) of the FGF1 gene. This alteration results from a A to G substitution at nucleotide position 140, causing the aspartic acid (D) at amino acid position 47 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.80	D;D;D;D;D;D;D;.;D;D;D;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	.;.;.;D;.;.;.;D;D;.;.;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.6	L;L;L;L;L;L;L;L;.;L;L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.3	N;.;.;.;.;N;N;D;D;N;N;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.016	D;.;.;.;.;D;D;D;D;D;D;D
Sift4G	Uncertain	0.057	T;T;T;T;T;T;T;T;D;T;T;.
Polyphen		0.12	B;B;B;B;B;B;B;D;.;B;B;.
Vest4		0.81
MutPred		0.48		Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);Gain of catalytic residue at D47 (P = 0.1164);
MVP		0.69
MPC		0.66
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.62
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.39		Position offset: -29

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1490756504; hg19: chr5-141993553;