Variant 14-28767488-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_005249.5(FOXG1):c.209A>G(p.Gln70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000023 in 871,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

FOXG1
NM_005249.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.693

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), FOXG1. . Trascript score misZ 3.7891 (greater than threshold 3.09). GenCC has associacion of gene with Rett syndrome, congenital variant, FOXG1 disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.088481426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FOXG1	NM_005249.5 linkuse as main transcript	c.209A>G	p.Gln70Arg	missense_variant	1/1	ENST00000313071.7	NP_005240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	Appris
FOXG1	ENST00000313071.7 linkuse as main transcript	c.209A>G	p.Gln70Arg	missense_variant	1/1	NM_005249.5	ENSP00000339004	P1
FOXG1	ENST00000706482.1 linkuse as main transcript	c.209A>G	p.Gln70Arg	missense_variant	2/2		ENSP00000516406	P1
LINC01551	ENST00000675861.1 linkuse as main transcript	n.374+1475A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

36220

Hom.:

AF XY:

0.00

AC XY:

AN XY:

22444

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000637

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000230

AC:

AN:

871404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

419006

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000264

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.28

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.36

M_CAP

Benign

0.071

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.18

REVEL

Benign

0.026

Sift

Benign

0.12

Sift4G

Benign

0.53

Polyphen

0.0030

Vest4

0.20

MutPred

0.32

Gain of catalytic residue at P65 (P = 5e-04);

MVP

0.014

ClinPred

0.024

GERP RS

0.93

Varity_R

0.045

gMVP

0.17

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over