3-192144092-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_004113.6(FGF12):c.463G>A(p.Gly155Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGF12 NM_004113.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.55

Genes affected

FGF12 (HGNC:3668): (fibroblast growth factor 12) 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 growth factor lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, this protein accumulated in the nucleus, but was not secreted. The specific function of this gene has not yet been determined. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34449315).
• BP6: Variant 3-192144092-C-T is Benign according to our data. Variant chr3-192144092-C-T is described in ClinVar as [Benign]. Clinvar id is 2075197.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.463G>A	p.Gly155Arg	missense_variant	6/6	ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.463G>A	p.Gly155Arg	missense_variant	6/6	1	NM_004113.6	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Oct 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.078	D
BayesDel_noAF	Benign	-0.13
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.34	T;T;T;T;T
MetaSVM	Benign	-0.61	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.1	N;N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.095	T;T;T;T;T
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.25	B;B;B;.;.
Vest4		0.38
MutPred		0.17		.;Loss of ubiquitination at K219 (P = 0.0111);.;.;.;
MVP		0.82
MPC		1.3
ClinPred		0.67	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr3-191861881;