19-58562225-AGG-CAA

Variant names:

• chr19-58562225-AGG-CAA
• NM_198055.2:c.2050_2052delCCTinsTTG
• MZF1 p.Pro684Leu

Variant summary

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

The NM_198055.2(MZF1):​c.2050_2052delCCTinsTTG​(p.Pro684Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P684H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MZF1 NM_198055.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 0 publications found

Genes affected

MZF1 (HGNC:13108): (myeloid zinc finger 1) Enables DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein homodimerization activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MZF1-AS1 (HGNC:51271): (MZF1 antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198055.2. 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
	MZF1	NM_198055.2	MANE Select	c.2050_2052delCCTinsTTG	p.Pro684Leu	missense	N/A	NP_932172.1	P28698-1
	MZF1	NM_003422.3		c.2050_2052delCCTinsTTG	p.Pro684Leu	missense	N/A	NP_003413.2
	MZF1	NM_001267033.2		c.*933_*935delCCTinsTTG		3_prime_UTR	Exon 6 of 6	NP_001253962.1	P28698-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MZF1	ENST00000215057.7	TSL:1 MANE Select	c.2050_2052delCCTinsTTG	p.Pro684Leu	missense	N/A	ENSP00000215057.1	P28698-1
	MZF1	ENST00000599369.5	TSL:1	c.2050_2052delCCTinsTTG	p.Pro684Leu	missense	N/A	ENSP00000469493.1	P28698-1
	MZF1	ENST00000594234.5	TSL:1	c.*933_*935delCCTinsTTG		3_prime_UTR	Exon 6 of 6	ENSP00000469378.1	P28698-3

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		-0.83

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: chr19-59073592;