rs587783629

chr14-28767410-AC-Achr14-28767410-AC-ACCchr14-28767410-AC-ACCC

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The NM_005249.5(FOXG1):c.136del(p.Gln46SerfsTer146) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000709 in 1,269,734 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: FOXG1 NM_005249.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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

Verdict is Likely_pathogenic. Variant got 8 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 248 pathogenic variants in the truncated region.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXG1	NM_005249.5	c.136del	p.Gln46SerfsTer146	frameshift_variant	1/1	ENST00000313071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXG1	ENST00000313071.7	c.136del	p.Gln46SerfsTer146	frameshift_variant	1/1		NM_005249.5	P1
FOXG1	ENST00000706482.1	c.136del	p.Gln46SerfsTer146	frameshift_variant	2/2			P1
LINC01551	ENST00000675861.1	n.374+1402del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000709 AC: 9 AN: 1269734 Hom.: 0 Cov.: 31 AF XY: 0.00000159 AC XY: 1 AN XY: 629702

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000624

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000381

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000233

Gnomad4 NFE exome AF: 0.00000502

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs587783629; hg19: chr14-29236616;