11-69703341-C-A

Variant names:

• chr11-69703341-C-A
• rs1854798896
• NM_005117.3:c.256G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005117.3(FGF19):​c.256G>T​(p.Ala86Ser) 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. 14/22 in silico tools predict 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. A86T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FGF19 NM_005117.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.89
• Publications: 0 publications found

Genes affected

FGF19 (HGNC:3675): (fibroblast growth factor 19) 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 is a high affinity, heparin dependent ligand for FGFR4. Expression of this gene was detected only in fetal but not adult brain tissue. Synergistic interaction of the chick homolog and Wnt-8c has been shown to be required for initiation of inner ear development. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34052894).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005117.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF19	NM_005117.3	MANE Select	c.256G>T	p.Ala86Ser	missense	Exon 2 of 3	NP_005108.1	O95750

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF19	ENST00000294312.4	TSL:1 MANE Select	c.256G>T	p.Ala86Ser	missense	Exon 2 of 3	ENSP00000294312.3	O95750
	FGF19	ENST00000911903.1		c.256G>T	p.Ala86Ser	missense	Exon 3 of 4	ENSP00000581962.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.43	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	0.93	L
PhyloP100		2.9
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.51	N
REVEL	Benign	0.27
Sift	Benign	0.23	T
Sift4G	Benign	0.21	T
Polyphen		0.42	B
Vest4		0.22
MutPred		0.37		Loss of ubiquitination at K83 (P = 0.1045)
MVP		0.88
MPC		1.0
ClinPred		0.58	D
GERP RS		4.0
Varity_R		0.42
gMVP		0.42
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs1854798896; hg19: chr11-69518109;