Variant summary

Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong

The NM_005249.5(FOXG1):c.214C>T(p.Gln72*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXG1
NM_005249.5 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:4

Conservation

PhyloP100: 1.96

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:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 18 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 262 pathogenic variants in the truncated region.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-28767493-C-T is Pathogenic according to our data. Variant chr14-28767493-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 487210.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.214C>T	p.Gln72*	stop_gained	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.214C>T	p.Gln72*	stop_gained	Exon 1 of 1	ENSP00000339004.3
FOXG1	ENST00000706482.1		c.214C>T	p.Gln72*	stop_gained	Exon 2 of 2	ENSP00000516406.1
LINC01551	ENST00000675861.1		n.374+1480C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

889596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

424224

African (AFR)

AF:

0.00

AC:

AN:

16618

American (AMR)

AF:

0.00

AC:

AN:

3734

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

7564

East Asian (EAS)

AF:

0.00

AC:

AN:

9736

South Asian (SAS)

AF:

0.00

AC:

AN:

21408

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1940

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

787972

Other (OTH)

AF:

0.00

AC:

AN:

30818

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Rett syndrome, congenital variant (3)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Pathogenic

0.44

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.22

PhyloP100

2.0

Vest4

0.47

GERP RS

1.1

Mutation Taster

=0/200

disease causing (ClinVar)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over