chr14-28767055-C-CTTT

Variant names:

• chr14-28767055-C-CTTT
• rs542787885
• NM_005249.5:c.-212_-210dupTTT

Variant summary

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

The NM_005249.5(FOXG1):​c.-212_-210dupTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene FOXG1 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXG1 NM_005249.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• 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

Specifications for FOXG1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.-212_-210dupTTT		5_prime_UTR	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.-212_-210dupTTT		5_prime_UTR	Exon 1 of 1	ENSP00000339004.3	P55316
	FOXG1	ENST00000706482.1		c.-212_-210dupTTT		5_prime_UTR	Exon 2 of 2	ENSP00000516406.1	P55316
	LINC01551	ENST00000675861.1		n.374+1055_374+1057dupTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 139686 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000290 AC: 1 AN: 3454 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1978

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 50

American (AMR) AF: 0.00 AC: 0 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22

East Asian (EAS) AF: 0.00 AC: 0 AN: 28

South Asian (SAS) AF: 0.00 AC: 0 AN: 470

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 16

European-Non Finnish (NFE) AF: 0.000394 AC: 1 AN: 2536

Other (OTH) AF: 0.00 AC: 0 AN: 106

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 139686 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 67592

African (AFR) AF: 0.00 AC: 0 AN: 38258

American (AMR) AF: 0.00 AC: 0 AN: 14062

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3290

East Asian (EAS) AF: 0.00 AC: 0 AN: 4854

South Asian (SAS) AF: 0.00 AC: 0 AN: 4418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64022

Other (OTH) AF: 0.00 AC: 0 AN: 1898

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.049

Splicing

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

Other links and lift over

dbSNP: rs542787885; hg19: chr14-29236261;