Variant 17-7439755-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004112.4(FGF11):c.135C>G(p.Ile45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FGF11
NM_004112.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0110

Variant links:

Genes affected

FGF11 (HGNC:3667): (fibroblast growth factor 11) 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. The function of this gene has not yet been determined. The expression pattern of the mouse homolog implies a role in nervous system development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

FGF11 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25020236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF11	NM_004112.4 linkuse as main transcript	c.135C>G	p.Ile45Met	missense_variant	1/5	ENST00000293829.9	NP_004103.1
FGF11	NR_130156.2 linkuse as main transcript	n.233+1225C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FGF11	ENST00000293829.9 linkuse as main transcript	c.135C>G	p.Ile45Met	missense_variant	1/5	1	NM_004112.4	ENSP00000293829	P1
FGF11	ENST00000575235.5 linkuse as main transcript	c.-180+1225C>G		intron_variant		1		ENSP00000459746
	ENST00000576615.1 linkuse as main transcript	n.70-336G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412362

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700844

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.135C>G (p.I45M) alteration is located in exon 1 (coding exon 1) of the FGF11 gene. This alteration results from a C to G substitution at nucleotide position 135, causing the isoleucine (I) at amino acid position 45 to be replaced by a methionine (M). 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

0.19

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

0.036

Eigen_PC

Benign

0.011

FATHMM_MKL

Benign

0.32

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.24

REVEL

Benign

0.26

Sift

Uncertain

0.023

Sift4G

Benign

0.080

Polyphen

0.94

Vest4

0.15

MutPred

0.34

Loss of stability (P = 0.0808);

MVP

0.83

MPC

1.8

ClinPred

0.66

GERP RS

2.9

Varity_R

0.15

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over