19-58562554-C-T

Position:

• chr19-58562554-C-T

Variant summary

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

The NM_198055.2(MZF1):​c.1723G>A​(p.Gly575Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MZF1 NM_198055.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

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=0.30977654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZF1	NM_198055.2	c.1723G>A	p.Gly575Ser	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.1723G>A	p.Gly575Ser	missense_variant	6/6	1	NM_198055.2	ENSP00000215057.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

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

Nov 25, 2024

The c.1723G>A (p.G575S) alteration is located in exon 6 (coding exon 5) of the MZF1 gene. This alteration results from a G to A substitution at nucleotide position 1723, causing the glycine (G) at amino acid position 575 to be replaced by a serine (S). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	T;T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.046
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-5.0	D;.
REVEL	Benign	0.14
Sift	Uncertain	0.0050	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.69	P;P
Vest4		0.40
MutPred		0.66		Loss of glycosylation at K576 (P = 0.1244);Loss of glycosylation at K576 (P = 0.1244);
MVP		0.41
MPC		1.8
ClinPred		0.95	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.45
gMVP		0.11

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: chr19-59073921; COSMIC: COSV53041352; COSMIC: COSV53041352;