Genetic Variant FOXG1:p.Pro82Leu (chr14-28767524-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005249.5(FOXG1):c.245C>T(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000111 in 904,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P82Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000011 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.424

Publications

0 publications found

Variant links:

Genes affected

FOXG1 (HGNC:3811): (forkhead box G1) This locus encodes a member of the fork-head transcription factor family. The encoded protein, which functions as a transcriptional repressor, is highly expressed in neural tissues during brain development. Mutations at this locus have been associated with Rett syndrome and a diverse spectrum of neurodevelopmental disorders defined as part of the FOXG1 syndrome. This gene is disregulated in many types of cancer and is the target of multiple microRNAs that regulate the proliferation of tumor cells. [provided by RefSeq, Jul 2020]

FOXG1 links:

LINC01551 (HGNC:19828): (long intergenic non-protein coding RNA 1551)

LINC01551 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11762798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005249.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.245C>T	p.Pro82Leu	missense	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.245C>T	p.Pro82Leu	missense	Exon 1 of 1	ENSP00000339004.3
FOXG1	ENST00000706482.1		c.245C>T	p.Pro82Leu	missense	Exon 2 of 2	ENSP00000516406.1
LINC01551	ENST00000675861.1		n.374+1511C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000111

AC:

AN:

904360

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

425952

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17448

American (AMR)

AF:

0.00

AC:

AN:

3614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7780

East Asian (EAS)

AF:

0.00

AC:

AN:

10480

South Asian (SAS)

AF:

0.00

AC:

AN:

17828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10256

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2050

European-Non Finnish (NFE)

AF:

0.00000125

AC:

AN:

802712

Other (OTH)

AF:

0.00

AC:

AN:

32192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.55

M_CAP

Benign

0.038

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

PhyloP100

-0.42

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.27

REVEL

Benign

0.040

Sift

Uncertain

0.0030

Sift4G

Benign

0.39

Polyphen

0.58

Vest4

0.21

MutPred

0.36

Gain of catalytic residue at P84 (P = 0.0016)

MVP

0.24

ClinPred

0.40

GERP RS

1.2

Varity_R

0.085

gMVP

0.17

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over