19-58562569-C-A

Variant names:

• chr19-58562569-C-A
• rs1486469107
• NM_198055.2:c.1708G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198055.2(MZF1):​c.1708G>T​(p.Ala570Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MZF1 NM_198055.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.04
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045500606).

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.1708G>T	p.Ala570Ser	missense	Exon 6 of 6	NP_932172.1	P28698-1
	MZF1	NM_003422.3		c.1708G>T	p.Ala570Ser	missense	Exon 6 of 6	NP_003413.2
	MZF1	NM_001267033.2		c.*591G>T		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.1708G>T	p.Ala570Ser	missense	Exon 6 of 6	ENSP00000215057.1	P28698-1
	MZF1	ENST00000599369.5	TSL:1	c.1708G>T	p.Ala570Ser	missense	Exon 6 of 6	ENSP00000469493.1	P28698-1
	MZF1	ENST00000594234.5	TSL:1	c.*591G>T		3_prime_UTR	Exon 6 of 6	ENSP00000469378.1	P28698-3

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1445438 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 717970

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 41974

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25806

East Asian (EAS) AF: 0.00 AC: 0 AN: 39132

South Asian (SAS) AF: 0.00 AC: 0 AN: 84548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106158

Other (OTH) AF: 0.00 AC: 0 AN: 59930

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.0
DANN	Benign	0.94
DEOGEN2	Benign	0.073	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.11	N
PhyloP100		-3.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.040
Sift	Benign	0.14	T
Sift4G	Benign	0.52	T
Polyphen		0.015	B
Vest4		0.064
MutPred		0.24		Gain of phosphorylation at A570 (P = 0.0441)
MVP		0.14
MPC		0.67
ClinPred		0.37	T
GERP RS		-0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.077
gMVP		0.041
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1486469107; hg19: chr19-59073936;