chr14-28767292-G-A

Variant names:

• chr14-28767292-G-A
• NM_005249.5:c.13G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005249.5(FOXG1):​c.13G>A​(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXG1 NM_005249.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	NM_005249.5	MANE Select	c.13G>A	p.Gly5Arg	missense	Exon 1 of 1	NP_005240.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXG1	ENST00000313071.7	TSL:6 MANE Select	c.13G>A	p.Gly5Arg	missense	Exon 1 of 1	ENSP00000339004.3	P55316
	FOXG1	ENST00000706482.1		c.13G>A	p.Gly5Arg	missense	Exon 2 of 2	ENSP00000516406.1	P55316
	LINC01551	ENST00000675861.1		n.374+1279G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1269052 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 629880

African (AFR) AF: 0.00 AC: 0 AN: 25850

American (AMR) AF: 0.00 AC: 0 AN: 33564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18820

East Asian (EAS) AF: 0.00 AC: 0 AN: 24946

South Asian (SAS) AF: 0.00 AC: 0 AN: 77274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4836

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 993150

Other (OTH) AF: 0.00 AC: 0 AN: 47744

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Rett syndrome, congenital variant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.096
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.88	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.70	D
MutationAssessor	Benign	0.81	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.62
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.34
MutPred		0.34		Gain of solvent accessibility (P = 0.0063)
MVP		0.86
ClinPred		0.78	D
GERP RS		2.0
Varity_R		0.35
gMVP		0.69
Mutation Taster		=14/86	disease causing

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

hg19: chr14-29236498;