19-58562093-C-G

Position:

• chr19-58562093-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198055.2(MZF1):​c.2184G>C​(p.Gln728His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MZF1 NM_198055.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.10

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33331358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZF1	NM_198055.2	c.2184G>C	p.Gln728His	missense_variant	6/6	ENST00000215057.7	NP_932172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MZF1	ENST00000215057.7	c.2184G>C	p.Gln728His	missense_variant	6/6	1	NM_198055.2	ENSP00000215057.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 19, 2024

The c.2184G>C (p.Q728H) alteration is located in exon 6 (coding exon 5) of the MZF1 gene. This alteration results from a G to C substitution at nucleotide position 2184, causing the glutamine (Q) at amino acid position 728 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	0.047
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.52	.;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.0	M;M
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.9	D;.
REVEL	Benign	0.062
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.011	D;D
Polyphen		0.99	D;D
Vest4		0.29
MutPred		0.44		Loss of MoRF binding (P = 0.1036);Loss of MoRF binding (P = 0.1036);
MVP		0.58
MPC		1.7
ClinPred		0.95	D
GERP RS		2.3
Varity_R		0.39
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-59073460;