20-23365248-GAG-CAA

Variant names:

• chr20-23365248-GAG-CAA
• NM_022482.5:c.865_867delGAGinsCAA
• GZF1 p.Glu289Gln

Variant summary

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

The NM_022482.5(GZF1):​c.865_867delGAGinsCAA​(p.Glu289Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GZF1 NM_022482.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

GZF1 (HGNC:15808): (GDNF inducible zinc finger protein 1) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GZF1 Gene-Disease associations (from GenCC):

• joint laxity, short stature, and myopia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• Larsen syndrome

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022482.5. 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
	GZF1	NM_022482.5	MANE Select	c.865_867delGAGinsCAA	p.Glu289Gln	missense	N/A	NP_071927.1	Q9H116-1
	GZF1	NM_001317012.2		c.865_867delGAGinsCAA	p.Glu289Gln	missense	N/A	NP_001303941.1	Q9H116-1
	GZF1	NM_001317019.1		c.865_867delGAGinsCAA	p.Glu289Gln	missense	N/A	NP_001303948.1	Q9H116

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GZF1	ENST00000338121.10	TSL:1 MANE Select	c.865_867delGAGinsCAA	p.Glu289Gln	missense	N/A	ENSP00000338290.5	Q9H116-1
	GZF1	ENST00000377051.2	TSL:1	c.865_867delGAGinsCAA	p.Glu289Gln	missense	N/A	ENSP00000366250.2	Q9H116-1
	GZF1	ENST00000907448.1		c.865_867delGAGinsCAA	p.Glu289Gln	missense	N/A	ENSP00000577507.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-23345885;