rs1555321206

chr14-28767449-ACCCGCCGCCG-Achr14-28767449-ACCCGCCGCCG-ACCCGCCGCCGCCCGCCGCCG

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_005249.5(FOXG1):c.177_186del(p.Pro60ArgfsTer129) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOXG1 NM_005249.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.977

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 9 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 243 pathogenic variants in the truncated region.
• PP5: Variant 14-28767449-ACCCGCCGCCG-A is Pathogenic according to our data. Variant chr14-28767449-ACCCGCCGCCG-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FOXG1	NM_005249.5	c.177_186del	p.Pro60ArgfsTer129	frameshift_variant	1/1	ENST00000313071.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXG1	ENST00000313071.7	c.177_186del	p.Pro60ArgfsTer129	frameshift_variant	1/1		NM_005249.5	P1
FOXG1	ENST00000706482.1	c.177_186del	p.Pro60ArgfsTer129	frameshift_variant	2/2			P1
LINC01551	ENST00000675861.1	n.374+1443_374+1452del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-29236655;