19-48757972-C-A

Position:

• chr19-48757972-C-A

Variant summary

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

The NM_019113.4(FGF21):​c.382C>A​(p.Leu128Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGF21 NM_019113.4 missense
• Clinical Significance: - - O:1
• Conservation: PhyloP100: 2.36

Genes affected

FGF21 (HGNC:3678): (fibroblast growth factor 21) Theis gene encodes 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. This protein is a secreted endocrine factor that functions as a major metabolic regulator. The encoded protein stimulates the uptake of glucose in adipose tissue. [provided by RefSeq, Mar 2016]

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
FGF21	NM_019113.4	c.382C>A	p.Leu128Ile	missense_variant	4/4	ENST00000593756.6	NP_061986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF21	ENST00000593756.6	c.382C>A	p.Leu128Ile	missense_variant	4/4	1	NM_019113.4	ENSP00000471477.1
FGF21	ENST00000222157.5	c.382C>A	p.Leu128Ile	missense_variant	3/3	1		ENSP00000222157.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

Submissions by phenotype

Neoplasm Other:1

-, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Jul 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.051	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.76	D;D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Uncertain	0.42	D
MutationAssessor	Pathogenic	3.3	M;M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.5	.;N
REVEL	Uncertain	0.43
Sift	Benign	0.19	.;T
Sift4G	Benign	0.20	T;T
Polyphen		0.99	D;D
Vest4		0.38
MutPred		0.50		Loss of disorder (P = 0.0976);Loss of disorder (P = 0.0976);
MVP		0.92
MPC		0.24
ClinPred		0.97	D
GERP RS		4.4
Varity_R		0.20
gMVP		0.31

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: chr19-49261229;